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1. Clinical Trial of TCM Collaborative Care Model in Axial Spondyloarthritis (AcuSpA)

Author: Duke-NUS Graduate Medical School, Saw Swee Hock School of Public Health, National University of Singapore, and Thong Chai Medical Institute Singapore
Published: 2024

2. Tele-rehabilitation Program: An Innovative and Sustainable Early Intervention Service for Children With Autism Spectrum Disorders

Author: Ministry of Health, Singapore and National University of Singapore, Saw Swee Hock School of Public Health
Published: 2023

3. Safety And Efficacy Of Hydroxychloroquine For At Risk Population (SHARP) Against COVID-19 (SHARP COVID-19)

Author: National Center for Infectious Diseases, Singapore Clinical Research Institute, Singapore Eye Research Institute, Saw Swee Hock School of Public Health, Duke-NUS Graduate Medical School, and Netherlands: Ministry of Health, Welfare and Sports
Published: 2020

4. Variation in Food Intakes, Physical Activity, and Psychological Stress on Fluctuations in 24-hr Plasma Glucose Levels

Author: National University of Singapore, Saw Swee Hock School of Public Health, National University Hospital, Singapore, and Ciaran Forde, Senior Principal Investigator
Published: 2020

5. Effect of Physical Therapy in Improving the Health of Patients With Diabetic Peripheral Neuropathy (DPN-QoL)

Author: National Medical Research Council (NMRC), Singapore, National University Hospital, Singapore, and Kavita Venkataraman, Assistant Professor, Saw Swee Hock School of Public Health, National University of Singapore (NUS) and National University Health System (NUHS)
Published: 2018

6. Association of triglyceride glucose index with prevalence and incidence of diabetic retinopathy in a Singaporean population

Author: Kumari Neelam, Khin Chaw Yu Aung, Keven Ang, Subramaniam Tavintharan, Chee Fang Sum, Su Chi Lim, Lee Kong Chian School of Medicine (LKCMedicine), Khoo Teck Puat Hospital, Admiralty Medical Centre, and Saw Swee Hock School of Public Health, NUS
Subjects: Ophthalmology, Diabetic Retinopathy, Triglyceride Glucose Index, Clinical Ophthalmology, Medicine [Science]
Abstract: Kumari Neelam,1,2,&ast; Khin Chaw Yu Aung,3,&ast; Keven Ang,3 Subramaniam Tavintharan,3,4 Chee Fang Sum,4 Su Chi Lim3â 6 1Department of Ophthalmology and Visual Sciences, Khoo Teck Puat Hospital, Singapore; 2Singapore Eye Research Institute, Singapore; 3Clinical Research Unit, Khoo Teck Puat Hospital, Singapore; 4Diabetes Centre, Admiralty Medical Centre, Singapore; 5Saw Swee Hock School of Public Health, National University of Singapore, Singapore; 6Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore&ast;These authors contributed equally to this workCorrespondence: Su Chi Lim, Clinical Research Unit, Khoo Teck Puat Hospital, 90 Yishun Central, 728828, Singapore, Email lim.su.chi@ktph.com.sgObjective: To examine the association of triglyceride glucose (TyG) index (product of fasting triglyceride and glucose) with prevalence and incidence of diabetic retinopathy (DR) in type 2 diabetes.Methods: 1339 patients from an ongoing Singapore Study of Macro-angiopathy and Micro-Vascular Reactivity in Type 2 Diabetes (SMART2D) were included in this study. Fasting triglyceride and glucose levels were quantified and color fundus photographs were assessed for DR presence and severity. Logistic regression models were used to evaluate associations of TyG index with DR prevalence and incidence (median follow-up period = 3.2 years).Results: Mean TyG index was higher in patients with DR than no DR (9.24Â± 0.7 versus 9.04Â± 0.6, p< 0.001). TyG index was significantly associated with DR prevalence (OR=1.4, CI 1.1â 1.7, p=0.002) and incidence (OR=1.8, CI 1.04â 2.9, p=0.03), after adjusting for confounders. In a stratified analysis, the association between TyG index and DR prevalence reached significance only in the subgroup with HbA1c levels < 7.0% (OR=2, CI 1.1â 3.8, p=0.03). TyG index significantly predicted DR prevalence and incidence with area under receiver operating curve as 0.77 (CI 0.74â 0.80, p < 0.001) and 0.66 (CI 0.57â 0.76, p value < 0.01), respectively.Conclusion: TyG index is a good predictor for DR prevalence and incidence. It can also be a secondary treatment target for patients with optimally controlled levels of HbA1c.Keywords: triglyceride glucose index, diabetic retinopathy, insulin resistance, prevalence, incidence
Published: 2023

7. Association between ambient air pollutants and upper respiratory tract infection and pneumonia disease burden in Thailand from 2000 to 2022: a high frequency ecological analysis

Author: Choo, Esther Li Wen, Janhavi, A., Koo, Joel Ruihan, Yim, Steve Hung Lam, Dickens, Borame L., Lim, Jue Tao, Lee Kong Chian School of Medicine (LKCMedicine), Asian School of the Environment, Saw Swee Hock School of Public Health, NUS, and Earth Observatory of Singapore
Subjects: Upper Respiratory Tract Infections, Medicine [Science], Pneumonia
Abstract: Background: A pertinent risk factor of upper respiratory tract infections (URTIs) and pneumonia is the exposure to major ambient air pollutants, with short term exposures to different air pollutants being shown to exacerbate several respiratory conditions. Methods: Here, using disease surveillance data comprising of reported disease case counts at the province level, high frequency ambient air pollutant and climate data in Thailand, we delineated the association between ambient air pollution and URTI/Pneumonia burden in Thailand from 2000 – 2022. We developed mixed-data sampling methods and estimation strategies to account for the high frequency nature of ambient air pollutant concentration data. This was used to evaluate the effects past concentrations of fine particulate matter (PM2.5), sulphur dioxide (SO2), and carbon monoxide (CO) and the number of disease case count, after controlling for the confounding meteorological and disease factors. Results: Across provinces, we found that past increases in CO, SO2, and PM2.5 concentration were associated to changes in URTI and pneumonia case counts, but the direction of their association mixed. The contributive burden of past ambient air pollutants on contemporaneous disease burden was also found to be larger than meteorological factors, and comparable to that of disease related factors. Conclusions: By developing a novel statistical methodology, we prevented subjective variable selection and discretization bias to detect associations, and provided a robust estimate on the effect of ambient air pollutants on URTI and pneumonia burden over a large spatial scale. Ministry of Education (MOE) Published version This research / project is supported by the Ministry of Education, Singapore, under its Academic Research Fund Tier 1 (RS04/22).
Published: 2023

8. Sociodemographic and behavioural factors of adherence to the no-screen guideline for toddlers among parents from the French nationwide Elfe birth cohort

Author: Lorraine Poncet, Mélèa Saïd, Malamine Gassama, Marie-Noëlle Dufourg, Falk Müller-Riemenschneider, Sandrine Lioret, Patricia Dargent-Molina, Marie-Aline Charles, Jonathan Y. Bernard, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Etude longitudinale française depuis l'enfance (UMS : Ined-Inserm-EFS) (ELFE), Institut national d'études démographiques (INED)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Berlin Institute of Health (BIH), Singapore Institute for Clinical Sciences [Singapour] (SICS), Agency for science, technology and research [Singapore] (A*STAR), and Bernard, Jonathan
Subjects: Adult, Parents, Nutrition and Dietetics, Parenting, Infant, Newborn, Child Behavior, Medicine (miscellaneous), Physical Therapy, Sports Therapy and Rehabilitation, Screen time, Sedentary behavior, Pregnancy, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, Humans, Female, Television, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Smartphone, Child, Tablet, Exercise, Birth cohort
Abstract: Background Excessive screen time in infancy and childhood has been associated with consequences on children’s development and health. International guidelines call for no screen time before age 2 years, whereas in France, the most prominent guidelines recommend no screen before age 3 years. However, data are lacking on parental adherence to the no-screen guideline for toddlers and factors of adherence in France. Using data from the French nationwide Elfe birth cohort, we estimated adherence to the no-screen guideline at age 2 years and examined related factors, including sociodemographic characteristics, parental leisure activities and screen time. Methods In 2011, 18,329 newborns and their parents were enrolled in 349 randomly selected maternity units across mainland France. At age 2 years, screen exposure of 13,117 toddlers was reported by parents in phone interviews. Data on sociodemographic characteristics, parental leisure activities and screen time were collected from both parents. Three patterns of parental leisure activities were derived by principal component analysis: literate (e.g.,reading), screen-based, and physical/artistic activities. Multivariable logistic regression models were used to examine the associations of sociodemographic characteristics, parental leisure activities and parental screen time with adherence to the no-screen guideline for toddlers. Results Overall, 1809/13,117 (13.5%) families adhered to the no-screen guideline for toddlers. Adherence was reduced with maternal age Conclusions Adherence to the no-screen guideline for toddlers in France was low. Parental leisure activities and parental screen time are major factors of adherence to the no-screen guideline and could be considered in targeted public health interventions.
Published: 2022
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9. Effects of Empagliflozin on Symptoms, Physical Limitations and Quality of Life in Patients Hospitalized for Acute Heart Failure - Results From the EMPULSE Trial

Author: Mikhail N. Kosiborod, Christiane E. Angermann, Sean P. Collins, John R. Teerlink, Piotr Ponikowski, Jan Biegus, Josep Comin-Colet, João Pedro Ferreira, Robert J. Mentz, Michael E. Nassif, Mitchell A. Psotka, Jasper Tromp, Martina Brueckmann, Jonathan P. Blatchford, Afshin Salsali, Adriaan A. Voors, Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of New South Wales [Sydney] (UNSW), University Hospital of Würzburg, University of Würzburg = Universität Würzburg, Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], University of California [San Francisco] (UC San Francisco), University of California (UC), Veterans Affairs Medical Center, San Francisco, California, University of Wrocław [Poland] (UWr), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], French-Clinical Research Infrastructure Network - F-CRIN [Paris] (Cardiovascular & Renal Clinical Trialists - CRCT ), Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Duke University Medical Center, Inova Heart and Vascular Institute, Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Boehringer Ingelheim International GmbH, Elderbrook Solutions GmbH on behalf of Boehringer Ingelheim Pharma GmbH & Co. KG, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, University Medical Center Groningen [Groningen] (UMCG), The EMPULSE (EMPagliflozin in patients hospitalized with acUte heart faiLure who have been StabilizEd) trial was funded by the Boehringer Ingelheim and Eli Lilly and Company DiabetesAlliance, BOZEC, Erwan, and Cardiovascular Centre (CVC)
Subjects: Questionnaires, Heart Failure, Malalts hospitalitzats, acute heart failure, Heart failure, SGLT2 inhibitor, Stroke Volume, Insuficiència cardíaca, Qüestionaris, Hospital patients, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Treatment Outcome, Glucosides, [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, Physiology (medical), Quality of Life, Humans, Farmacologia cardiovascular, Cardiovascular pharmacology, Benzhydryl Compounds, Cardiology and Cardiovascular Medicine
Abstract: Background: Patients hospitalized for acute heart failure experience poor health status, including a high burden of symptoms and physical limitations, and poor quality of life. SGLT2 (sodium-glucose cotransporter 2) inhibitors improve health status in chronic heart failure, but their effect on these outcomes in acute heart failure is not well characterized. We investigated the effects of the SGLT2 inhibitor empagliflozin on symptoms, physical limitations, and quality of life, using the Kansas City Cardiomyopathy Questionnaire (KCCQ) in the EMPULSE trial (Empagliflozin in Patients Hospitalized With Acute Heart Failure Who Have Been Stabilized). Methods: Patients hospitalized for acute heart failure were randomized to empagliflozin 10 mg daily or placebo for 90 days. The KCCQ was assessed at randomization and 15, 30, and 90 days. The effects of empagliflozin on the primary end point of clinical benefit (hierarchical composite of all-cause death, heart failure events, and a 5-point or greater difference in KCCQ Total Symptom Score [TSS] change from baseline to 90 days) were examined post hoc across the tertiles of baseline KCCQ-TSS. In prespecified analyses, changes (randomization to day 90) in KCCQ domains, including TSS, physical limitations, quality of life, clinical summary, and overall summary scores were evaluated using a repeated measures model. Results: In total, 530 patients were randomized (265 each arm). Baseline KCCQ-TSS was low overall (mean [SD], 40.8 [24.0] points). Empagliflozin-treated patients experienced greater clinical benefit across the range of KCCQ-TSS, with no treatment effect heterogeneity (win ratio [95% CIs] from lowest to highest tertile: 1.49 [1.01–2.20], 1.37 [0.94–1.99], and 1.48 [1.00–2.20], respectively; P for interaction=0.94). Beneficial effects of empagliflozin on health status were observed as early as 15 days and persisted through 90 days, at which point empagliflozin-treated patients experienced a greater improvement in KCCQ TSS, physical limitations, quality of life, clinical summary, and overall summary (placebo-adjusted mean differences [95% CI]: 4.45 [95% CI, 0.32–8.59], P =0.03; 4.80 [95% CI, 0.00–9.61], P =0.05; 4.66 [95% CI, 0.32–9.01], P =0.04; 4.85 [95% CI, 0.77–8.92], P =0.02; and 4.40 points [95% CI, 0.33–8.48], P =0.03, respectively). Conclusions: Initiation of empagliflozin in patients hospitalized for acute heart failure produced clinical benefit regardless of the degree of symptomatic impairment at baseline, and improved symptoms, physical limitations, and quality of life, with benefits seen as early as 15 days and maintained through 90 days. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT0415775.
Published: 2022
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10. Viral Dynamics and Immune Correlates of Coronavirus Disease 2019 (COVID-19) Severity

Author: Young, Barnaby E, Ong, Sean W X, Ng, Lisa F P, Anderson, Danielle E, Chia, Wan Ni, Chia, Po Ying, Ang, Li Wei, Mak, Tze-Minn, Kalimuddin, Shirin, Chai, Louis Yi Ann, Pada, Surinder, Tan, Seow Yen, Sun, Louisa, Parthasarathy, Purnima, Fong, Siew-Wai, Chan, Yi-Hao, Tan, Chee Wah, Lee, Bernett, Rötzschke, Olaf, Ding, Ying, Tambyah, Paul, Low, Jenny G H, Cui, Lin, Barkham, Timothy, Lin, Raymond Tzer Pin, Leo, Yee-Sin, Renia, Laurent, Wang, Lin-Fa, Lye, David Chien, Lim, Poh Lian, Peng Ang, Brenda Sze, Lee, Cheng Chuan, U Lee, Lawrence Soon, Ling, Li Min, Ng, Oon Tek, Chan, Monica, Marimuthu, Kalisvar, Vasoo, Shawn, Wong, Chen Seong, Lee, Tau Hong, Sadarangani, Sapna, Lin, Ray Junhao, Sadasiv, Mucheli Sharavan, Ling Ng, Deborah Hee, Choy, Chiaw Yee, En Tan, Glorijoy Shi, Tan, Yu Kit, Sutjipto, Stephanie, Lee, Pei Hua, Tay, Jun Yang, Yeo, Tsin Wen, Khoo, Bo Yan, Tay, Woo Chiao, Ng, Gabrielle, Mah, Yun Yuan, Tan, Wilnard, De, Partha Pratim, Pooja, Rao, Chia, Jonathan W Z, Constance Chen, Yuan Yi, Mendis, Shehara, Toh, Boon Kiat, Choon Fong, Raymond Kok, Lin Oh, Helen May, Fong Chien, Jaime Mei, Shafi, Humaira, Cheong, Hau Yiang, Tan, Thean Yen, Tan, Thuan Tong, Tan, Ban Hock, Wijaya, Limin, Venkatachalam, Indumathi, Chua, Ying Ying, Zhi Cherng, Benjamin Pei, Zi Chan, Yvonne Fu, Wong, Hei Man, Thien, Siew Yee, Meng Goh, Kenneth Choon, Ling Tan, Shireen Yan, Ean Oon, Lynette Lin, Chan, Kian Sing, Lin, Li, Gin Chan, Douglas Su, Ooi, Say Tat, Narayana, Deepak Rama, Somani, Jyoti, Ling Oon, Jolene Ee, Yan, Gabriel Zherong, Allen, David Michael, Jureen, Roland, Yan, Benedict, Foo, Randy, Kang, Adrian, Sivalingam, Velraj, How, Wilson, Fernandez, Norman Leo, Yeo, Nicholas Kim-Wah, Chee, Rhonda Sin-Ling, Amrun, Siti Naqiah, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, NUS, and Saw Swee Hock School of Public Health, NUS
Subjects: 0301 basic medicine, Microbiology (medical), biology, Viral culture, business.industry, 030106 microbiology, COVID-19, medicine.disease, 03 medical and health sciences, Pneumonia, 0302 clinical medicine, Infectious Diseases, Immune system, Immunoglobulin M, Viral pneumonia, Immunology, Severity of illness, medicine, biology.protein, Cytokines, Medicine [Science], 030212 general & internal medicine, Seroconversion, Antibody, business
Abstract: Background Key knowledge gaps remain in the understanding of viral dynamics and immune response of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection. Methods We evaluated these characteristics and established their association with clinical severity in a prospective observational cohort study of 100 patients with PCR-confirmed SARS-CoV-2 infection (mean age, 46 years; 56% male; 38% with comorbidities). Respiratory samples (n = 74) were collected for viral culture, serum samples for measurement of IgM/IgG levels (n = 30), and plasma samples for levels of inflammatory cytokines and chemokines (n = 81). Disease severity was correlated with results from viral culture, serologic testing, and immune markers. Results Fifty-seven (57%) patients developed viral pneumonia, of whom 20 (20%) required supplemental oxygen, including 12 (12%) with invasive mechanical ventilation. Viral culture from respiratory samples was positive for 19 of 74 patients (26%). No virus was isolated when the PCR cycle threshold (Ct) value was >30 or >14 days after symptom onset. Seroconversion occurred at a median (IQR) of 12.5 (9–18) days for IgM and 15.0 (12–20) days for IgG; 54/62 patients (87.1%) sampled at day 14 or later seroconverted. Severe infections were associated with earlier seroconversion and higher peak IgM and IgG levels. Levels of IP-10, HGF, IL-6, MCP-1, MIP-1α, IL-12p70, IL-18, VEGF-A, PDGF-BB, and IL-1RA significantly correlated with disease severity. Conclusions We found virus viability was associated with lower PCR Ct value in early illness. A stronger antibody response was associated with disease severity. The overactive proinflammatory immune signatures offer targets for host-directed immunotherapy, which should be evaluated in randomized controlled trials.
Published: 2020
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11. Family-focused contextual factors associated with lifestyle patterns in young children from two mother-offspring cohorts: GUSTO and EDEN

Author: Airu Chia, Alexandra Descarpentrie, Rene N. Cheong, Jia Ying Toh, Padmapriya Natarajan, Ray Sugianto, Shirong Cai, Cécilia Saldanha-Gomes, Patricia Dargent-Molina, Blandine de Lauzon-Guillain, Sabine Plancoulaine, Carla Lança, Seang Mei Saw, Keith M. Godfrey, Lynette P. Shek, Kok Hian Tan, Marie-Aline Charles, Yap Seng Chong, Barbara Heude, Johan G. Eriksson, Falk Müller-Riemenschneider, Sandrine Lioret, Mary F.-F. Chong, Jonathan Y. Bernard, Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université (HESAM)-HESAM Université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPC)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Singapore Institute for Clinical Sciences [Singapour] (SICS), Singapore Eye Research Institute [Singapore] (SERI), NIHR Southampton Biomedical Research Centre, Yong Loo Lin School of Medicine [Singapore], KK Women's and Children's Hospital [Singapore], This research is supported by the Paris‐NUS grant (ANR‐18‐IDEX‐0001).The EDEN study is supported by Foundation for Medical Research (FRM), National Agency for Research (ANR), National Institute for Research in Public Health (IRESP: TGIR cohorte santé 2008 program), French Ministry of Health (DGS), French Ministry of Research, INSERM Bone and Joint Diseases National Research (PRO‐A), and Human Nutrition National Research Programs, Paris‐Sud University, Nestlé, French National Institute for Population Health Surveillance (InVS.), French National Institute for Health Education (INPES), the European Union FP7 programmes (FP7/2007–2013, HELIX, ESCAPE, ENRIECO, Medall projects), Diabetes National Research Program (through a collaborationwith the French Association of Diabetic Patients (AFD)), French Agency for Environmental Health Safety (now ANSES), Mutuelle Générale de l’Education Nationale a complementary health insurance (MGEN), French National Agency for Food Security, French‐speaking Association for the Study of Diabetes and Metabolism (ALFEDIAM).The GUSTO study is supported by the Singapore National Research Founda‐ tion under its Translational and Clinical Research Flagship Programme and administered by the Singapore Ministry of Health’s National Medical Research Council, Singapore ‐ NMRC/TCR/004‐NUS/2008, NMRC/TCR/012‐NUHS/2014. Additional funding is provided by the Singapore Institute for Clinical Sciences, Agency for Science Technology and Research, Singapore. KMG is supported by the UK Medical Research Council (MC_UU_12011/4), the National Institute for Health Research (NIHR Senior Investigator (NF‐SI‐0515‐10042) and NIHR South‐ ampton Biomedical Research Centre (IS‐BRC‐1215‐20004)), the European Union (Erasmus+ Programme ImpENSA 598488‐EPP‐1‐2018‐1‐DE‐EPPKA2‐ CBHE‐JP) and the British Heart Foundation (RG/15/17/3174). The funders had no role in the design of the study and collection, analysis, and interpretation of data and in writing the manuscript., and ANR-18-IDEX-0001,Université de Paris,Université de Paris(2018)
Subjects: Male, QUESTIONNAIRE, Mothers, Medicine (miscellaneous), Physical Therapy, Sports Therapy and Rehabilitation, Pregnancy, FOOD, Humans, Hierarchical analysis, VALIDITY, Child, Life Style, Nutrition and Dietetics, Physical activity, Preschool children, 1184 Genetics, developmental biology, physiology, Feeding Behavior, ADULTS, Screen time, Diet, DIETARY PATTERNS, PHYSICAL-ACTIVITY, Lifestyle patterns, Child, Preschool, OBESITY, 3121 General medicine, internal medicine and other clinical medicine, Female, Television, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Family ecological model, Snacks, 3143 Nutrition, TRANSITION
Abstract: Background Integrated patterns of energy balance-related behaviours of preschool children in Asia are sparse, with few comparative analyses. Purpose Using cohorts in Singapore (GUSTO) and France (EDEN), we characterized lifestyle patterns of children and investigated their associations with family-focused contextual factors. Methods Ten behavioural variables related to child’s diet, walking, outdoor play and screen time were ascertained by parental questionnaires at age 5–6 years. Using principal component analysis, sex-specific lifestyle patterns were derived independently for 630 GUSTO and 989 EDEN children. Contextual variables were organised into distal (family socio-economics, demographics), intermediate (parental health, lifestyle habits) and proximal (parent-child interaction factors) levels of influence and analysed with hierarchical linear regression. Results Three broadly similar lifestyle patterns were identified in both cohorts: “discretionary consumption and high screen time”, “fruit, vegetables, and low screen time” and “high outdoor playtime and walking”. The latter two patterns showed small differences between cohorts and sexes. The “discretionary consumption and high screen time” pattern was consistently similar in both cohorts; distal associated factors were lower maternal education (EDEN boys), no younger siblings (GUSTO boys) and Malay/Indian ethnicity (GUSTO), while intermediate and proximal associated factors in both cohorts and sexes were poor maternal diets during pregnancy, parents allowing high child control over food intake, snacking between meals and having television on while eating. Conclusions Three similar lifestyle patterns were observed among preschool children in Singapore and France. There were more common associated proximal factors than distal ones. Cohort specific family-focused contextual factors likely reflect differences in social and cultural settings. Findings will aid development of strategies to improve child health.
Published: 2022
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12. Prospective associations of lifestyle patterns in early childhood with socio‐emotional and behavioural development and BMI : An outcome‐wide analysis of the EDEN mother–child cohort

Author: Alexandra Descarpentrie, Jonathan Y. Bernard, Stephanie Vandentorren, Maria Melchior, Cédric Galéra, Airu Chia, Mary F.‐F. Chong, Marie‐Aline Charles, Barbara Heude, Sandrine Lioret, Bernard, Jonathan, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Singapore Institute for Clinical Sciences [Singapour] (SICS), Agency for science, technology and research [Singapore] (A*STAR), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Santé publique France - French National Public Health Agency [Saint-Maurice, France], Equipe de Recherche en Epidémiologie Sociale [iPLesp] (ERES), Institut Pierre Louis d'Epidémiologie et de Santé Publique (iPLESP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU), Centre hospitalier Charles Perrens [Bordeaux], Saw Swee Hock School of Public Health [Singapore, Singapore], and National University of Singapore (NUS)
Subjects: obesity, children, Epidemiology, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Pediatrics, Perinatology and Child Health, lifestyle patterns, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, socio-emotional and behavioural development, outcome-wide epidemiology
Abstract: International audience; Background: Children's energy balance-related behaviours (EBRB), comprising diet, screen time, physical activity, and sleep, combine into "lifestyle patterns", which may exert a synergistic effect on health. To date, studies investigating this synergy have primarily focused on obesity risk, without addressing other facets of health.Objectives: To examine the prospective associations of preschoolers' lifestyle patterns with socio-emotional, behavioural, and body mass index (BMI) outcomes at 8 years.Methods: Participants were 876 children from the EDEN mother-child cohort. Three lifestyle patterns (unhealthy, healthy, and mixed) were previously identified at age 5, separately in boys and girls. At age 8, height and weight measures generated BMI z-scores while social-emotional and behavioural development was assessed by parents using the Strengths and Difficulties Questionnaire (SDQ). Drawing from the outcome-wide approach, sex- and outcome-specific adjusted linear regressions were fitted.Results: Boys' adherence to a healthy lifestyle pattern (combining a nutrient-dense diet and limited screen time) at 5 years was positively associated with prosocial behaviours (β = 0.14; 95% confidence interval [CI] 0.01, 0.26) and inversely related to hyperactivity-inattention symptoms (β = -0.12; 95% CI -0.23, -0.01) at 8 years. Girls' mixed lifestyle pattern (sugar or artificially sweetened beverages, high screen, physical activity and low sleep times) was associated with prosocial behaviours (β = 0.12; 95% CI 0.01, 0.23). There was no evidence of associations between lifestyle patterns and BMI z-scores.Conclusions: Findings suggest synergistic benefits of engaging in a combination of optimal EBRBs, especially in boys, and support intervention efforts at preschool age to enhance some dimensions of their later socio-emotional and behavioural development.
Published: 2022
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13. The SGLT2 inhibitor empagliflozin in patients hospitalized for acute heart failure

Author: Voors, Adriaan, Angermann, Christiane, Teerlink, John, Collins, Sean, Kosiborod, Mikhail, Biegus, Jan, Ferreira, João Pedro, Nassif, Michael, Psotka, Mitchell, Tromp, Jasper, Borleffs, C. Jan Willem, Ma, Changsheng, Comin-Colet, Joseph, Fu, Michael, Janssens, Stefan, Kiss, Robert, Mentz, Robert, Sakata, Yasushi, Schirmer, Henrik, Schou, Morten, Schulze, P. Christian, Spinarova, Lenka, Volterrani, Maurizio, Wranicz, Jerzy, Zeymer, Uwe, Zieroth, Shelley, Brueckmann, Martina, Blatchford, Jonathan, Salsali, Afshin, Ponikowski, Piotr, University Medical Center Groningen [Groningen] (UMCG), University Hospital of Würzburg, University of California [San Francisco] (UC San Francisco), University of California (UC), Vanderbilt University Medical Center [Nashville], Vanderbilt University [Nashville], Saint Luke's Mid America Heart Institute, The George Institute for Global Health [Sydney] (GIGH), The University of Sydney, University of New South Wales [Sydney] (UNSW), University of Missouri School of Medicine, University of Missouri System, Wrocław Medical University, Défaillance Cardiovasculaire Aiguë et Chronique (DCAC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Centre d'investigation clinique plurithématique Pierre Drouin [Nancy] (CIC-P), Centre d'investigation clinique [Nancy] (CIC), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy] (INI-CRCT), Institut Lorrain du Coeur et des Vaisseaux Louis Mathieu [Nancy], Faculdade de Medicina da Universidade do Porto (FMUP), Universidade do Porto = University of Porto, Inova Heart and Vascular Institute, Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Haga Teaching Hospital [Hague], Capital University of Medical Sciences [Beijing] (CUMS), Institut d'Investigació Biomèdica de Bellvitge [Barcelone] (IDIBELL), Sahlgrenska University Hospital [Gothenburg], Department of Cardiovascular Sciences [Leuven], Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Department of Cardiology, Military Hospital [Budapest], Duke University Medical Center, Osaka University [Osaka], Akershus University Hospital [Lørenskog], Gentofte University Hospital, Jena University Hospital [Jena], Faculty of Medicine [Brno] (MED / MUNI), Masaryk University [Brno] (MUNI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS San Raffaele Pisana), Medical University of Łódź (MUL), Klinikum Ludwigshafen [Germany], University of Manitoba [Winnipeg], Boehringer Ingelheim International GmbH, Medizinische Fakultät Mannheim, Boehringer Ingelheim Pharma GmbH & Co. KG, Boehringer Ingelheim Pharmaceuticals, Inc, Ridgefield, Rutgers, The State University of New Jersey [New Brunswick] (RU), Rutgers University System (Rutgers), The sponsors of the trial were Boehringer Ingelheim and Eli Lilly and Company, and BOZEC, Erwan
Subjects: [SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system, [SDV.MHEP.CSC] Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system
Abstract: International audience; The sodium–glucose cotransporter 2 inhibitor empagliflozin reduces the risk of cardiovascular death or heart failure hospitalization in patients with chronic heart failure, but whether empagliflozin also improves clinical outcomes when initiated in patients who are hospitalized for acute heart failure is unknown. In this double-blind trial (EMPULSE; NCT04157751 ), 530 patients with a primary diagnosis of acute de novo or decompensated chronic heart failure regardless of left ventricular ejection fraction were randomly assigned to receive empagliflozin 10 mg once daily or placebo. Patients were randomized in-hospital when clinically stable (median time from hospital admission to randomization, 3 days) and were treated for up to 90 days. The primary outcome of the trial was clinical benefit, defined as a hierarchical composite of death from any cause, number of heart failure events and time to first heart failure event, or a 5 point or greater difference in change from baseline in the Kansas City Cardiomyopathy Questionnaire Total Symptom Score at 90 days, as assessed using a win ratio. More patients treated with empagliflozin had clinical benefit compared with placebo (stratified win ratio, 1.36; 95% confidence interval, 1.09–1.68; P = 0.0054), meeting the primary endpoint. Clinical benefit was observed for both acute de novo and decompensated chronic heart failure and was observed regardless of ejection fraction or the presence or absence of diabetes. Empagliflozin was well tolerated; serious adverse events were reported in 32.3% and 43.6% of the empagliflozin- and placebo-treated patients, respectively. These findings indicate that initiation of empagliflozin in patients hospitalized for acute heart failure is well tolerated and results in significant clinical benefit in the 90 days after starting treatment.
Published: 2022
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14. Seroprevalence of IgG antibodies against diphtheria antitoxin among migrant workers in Singapore, 2016–2019

Author: Li Wei Ang, Qi Gao, Lin Cui, Aysha Farwin, Matthias Paul Han Sim Toh, Irving Charles Boudville, Mark I-Cheng Chen, Angela Chow, Raymond Tzer-Pin Lin, Vernon Jian Ming Lee, Yee Sin Leo, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Saw Swee Hock School of Public Health, National University of Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, National University of Singapore, Singapore
Subjects: Adult, Transients and Migrants, Singapore, Basic protection, Diphtheria Toxoid, Research, Public Health, Environmental and Occupational Health, Immunity, Seroprevalence, Diphtheria, Migrant workers, complex mixtures, Antibodies, Bacterial, Diphtheria Antitoxin, Seroepidemiologic Studies, Immunoglobulin G, Humans, Medicine [Science], Public aspects of medicine, RA1-1270, geographic locations, Vaccination coverage
Abstract: Background: Since the last local case of diphtheria in 1992, there had not been any case in Singapore until an autochthonous case was reported in 2017. This fatal diphtheria case of a migrant worker raised concerns about the potential re-emergence of locally transmitted toxigenic diphtheria in Singapore. We conducted a seroprevalence study to assess the immunity levels to diphtheria among migrant workers in Singapore. Methods: Residual sera from migrant workers who hailed from Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines were tested for anti-diphtheria toxoid immunoglobulin G (IgG) antibodies. These migrant workers previously participated in a survey between 2016 and 2019 and had provided blood samples as part of the survey procedure. Results: A total of 2176 migrant workers were included in the study. Their overall mean age was 27.1 years (standard deviation 5.0), range was 20–43 years. The proportion having at least basic protection against diphtheria (antitoxin titres ≥ 0.01 IU/ml) ranged from 77.9% (95% confidence interval [CI] 72.8 – 82.3%) among migrant workers from Bangladesh to 96.7% (95% CI 92.5 – 98.6%) in those hailing from Malaysia. The proportion showing full protection (antitoxin titres ≥ 0.10 IU/ml) ranged from 10.1% (95% CI 6.5 – 15.4%) in Chinese workers to 23.0% (95% CI 17.1 – 30.3%) in Malaysian workers. There were no significant differences in the proportion with at least basic protection across birth cohorts, except for those from Bangladesh where the seroprevalence was significantly lower in younger migrant workers born after 1989. Conclusions: The proportions having at least basic protection against diphtheria in migrant workers from five out of seven Asian countries (India, Indonesia, Malaysia, Myanmar and the Philippines) were higher than 85%, the threshold for diphtheria herd immunity. Seroprevalence surveys should be conducted periodically to assess the level of immunity against diphtheria and other vaccine preventable diseases in migrant worker population, so that appropriate interventions such as booster vaccination can be implemented proactively to prevent sporadic outbreaks. Published version MICC was supported by the Ministry of Health, Singapore, under the Communicable Diseases – Public Health Research Grant (grant number MOHCS‑ 15MAR001) for sample collection. Laboratory testing for the seroprevalence of diphtheria among migrant workers was supported by the National Public Health Laboratory.
Published: 2022

15. Fending off Delta - hospital measures to reduce nosocomial transmission of COVID-19

Author: Rachel Hui Fen LIM, Htet Lin HTUN, Anthony Lianjie LI, Huiling GUO, Win Mar KYAW, AUNG Aung Hein, Brenda ANG, Angela CHOW, Lee Kong Chian School of Medicine (LKCMedicine), Tan Tock Seng Hospital, and Saw Swee Hock School of Public Health, National University of Singapore
Subjects: Microbiology (medical), Cross Infection, SARS-CoV-2, COVID-19, General Medicine, staff surveillance, Hospitals, Article, Cohort Studies, Infectious Diseases, Delta, personal protective equipment, rostered routine testing, Humans, Medicine [Science]
Abstract: Objectives: Following the emergence of the Delta variant of SARS-CoV-2 in Singapore, our hospital experienced a Delta-linked ward cluster. In this study, we review the enhanced strategies in preventing nosocomial transmission of COVID-19 following widespread community transmission of the Delta variant. Methods: We conducted a cohort study on exposures to unexpected COVID-19 cases for which contact tracing was initiated from June 2021 to October 2021. Strategies evaluated included upgraded personal protective equipment (PPE) and rostered routine testing (RRT) for staff and patients, surveillance of staff with acute respiratory illness (ARI), and expanded quarantining and testing for contacts of identified cases. Results: From 193 unexpected COVID-19 exposures, 2,573 staff, 542 patients, and 128 visitor contacts were traced. Four staff contacts subsequently had SARS-CoV-2 infection. Two were likely from exposure in community settings, whereas 2 had exposure to the same COVID-19 positive staff in the hospital, forming the only hospital cluster. One inpatient had a nosocomial infection, possibly from visitors. The SARS-CoV-2 detection rate among staff was 0.3% (of 11,200 staff) from biweekly RRT and 2.5% (of 3,675 staff) from ARI surveillance. Conclusion: Enhanced hospital measures, including upgraded PPE and RRT for staff and patients, staff sickness surveillance, and more rigorous management of contacts of COVID-19 cases, were likely to have reduced nosocomial transmission amid the Delta variant. Published version
Published: 2022

16. Prevalence of measles antibodies among migrant workers in Singapore: a serological study to identify susceptible population subgroups

Author: Li Wei Ang, Qi Gao, Lin Cui, Aysha Farwin, Matthias Paul Han Sim Toh, Irving Charles Boudville, Mark I-Cheng Chen, Angela Chow, Raymond Tzer-Pin Lin, Vernon Jian Ming Lee, Yee Sin Leo, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Saw Swee Hock School of Public Health, National University of Singapore, Tan Tock Seng Hospital, and Yong Loo Lin School of Medicine, National University of Singapore
Subjects: Male, Transients and Migrants, Singapore, Research, Immunity, Infectious and parasitic diseases, RC109-216, Middle Aged, Antibodies, Viral, Migrant workers, Infectious Diseases, Seroepidemiologic Studies, Prevalence, Humans, Female, Medicine [Science], Vaccination coverage, Measles
Abstract: Background: In 2019, two clusters of measles cases were reported in migrant worker dormitories in Singapore. We conducted a seroprevalence study to measure the level of susceptibility to measles among migrant workers in Singapore. Methods: Our study involved residual sera of migrant workers from seven Asian countries (Bangladesh, China, India, Indonesia, Malaysia, Myanmar and the Philippines) who had participated in a survey between 2016 and 2019. Immunoglobulin G (IgG) antibody levels were first measured using a commercial enzyme-linked immunosorbent assay (ELISA) test kit. Those with equivocal or negative IgG results were further evaluated using plaque reduction neutralization test (PRNT). Results: A total of 2234 migrant workers aged 20–49 years were included in the study. The overall prevalence of measles IgG antibodies among migrant workers from the seven Asian countries was 90.5% (95% confidence interval 89.2–91.6%). The country-specific seroprevalence ranged from 80.3 to 94.0%. The seroprevalence was significantly higher among migrant workers born in 1965–1989 than those born in 1990–1999 (95.3% vs. 86.6%, p < 0.0005), whereas there was no significant difference by gender (90.8% in men vs. 89.9% in women, p = 0.508). 195 out of 213 samples with equivocal or negative ELISA results were tested positive using PRNT. Conclusion: The IgG seroprevalence in migrant workers was below the herd immunity threshold of 95% for measles. Sporadic outbreaks may occur in susceptible individuals due to high transmissibility of measles virus. Seroprevalence surveys can help identify susceptible subgroups for vaccination. Ministry of Health (MOH) Published version Sample collection was supported by the Ministry of Health, Singapore, under the Communicable Diseases—Public Health Research Grant (Grant Number MOHCS15MAR001). Laboratory testing for the seroprevalence of measles in migrant workers was supported by the National Public Health Laboratory.
Published: 2022

17. Data-Driven Analysis of COVID-19 Reveals Persistent Immune Abnormalities in Convalescent Severe Individuals

Author: Jackwee Lim, Kia Joo Puan, Liang Wei Wang, Karen Wei Weng Teng, Chiew Yee Loh, Kim Peng Tan, Guillaume Carissimo, Yi-Hao Chan, Chek Meng Poh, Cheryl Yi-Pin Lee, Siew-Wai Fong, Nicholas Kim-Wah Yeo, Rhonda Sin-Ling Chee, Siti Naqiah Amrun, Zi Wei Chang, Matthew Zirui Tay, Anthony Torres-Ruesta, Norman Leo Fernandez, Wilson How, Anand Kumar Andiappan, Wendy Lee, Kaibo Duan, Seow-Yen Tan, Gabriel Yan, Shirin Kalimuddin, David Chien Lye, Yee-Sin Leo, Sean W. X. Ong, Barnaby E. Young, Laurent Renia, Lisa F. P. Ng, Bernett Lee, Olaf Rötzschke, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, and Saw Swee Hock School of Public Health, National University of Singapore
Subjects: Adult, Male, Immunology, Cytokine Profile, severity, Inflammation, cytokine profile, CD38, active infection, Cohort Studies, Post-Acute COVID-19 Syndrome, Immune system, immunophenotyping, medicine, Humans, Immunology and Allergy, Medicine [Science], Aged, Original Research, CD86, SARS-CoV-2, business.industry, COVID-19, Convalescence, Middle Aged, immune recovery, RC581-607, Vascular endothelial growth factor A, inflammation, SARS – CoV – 2, Female, Hepatocyte growth factor, Interleukin-3 receptor, Immunologic diseases. Allergy, medicine.symptom, business, CD8, medicine.drug
Abstract: Severe SARS-CoV-2 infection can trigger uncontrolled innate and adaptive immune responses, which are commonly associated with lymphopenia and increased neutrophil counts. However, whether the immune abnormalities observed in mild to severely infected patients persist into convalescence remains unclear. Herein, comparisons were drawn between the immune responses of COVID-19 infected and convalescent adults. Strikingly, survivors of severe COVID-19 had decreased proportions of NKT and Vδ2 T cells, and increased proportions of low-density neutrophils, IgA+/CD86+/CD123+ non-classical monocytes and hyperactivated HLADR+CD38+ CD8+ T cells, and elevated levels of pro-inflammatory cytokines such as hepatocyte growth factor and vascular endothelial growth factor A, long after virus clearance. Our study suggests potential immune correlates of "long COVID-19", and defines key cells and cytokines that delineate true and quasi-convalescent states. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Published version This work was supported by A*STAR Infectious Diseases Labs and Singapore Immunology Network (SIgN) core research grants, and the A*STAR COVID-19 Research funding (H/20/04/g1/006) provided to SIgN by the Biomedical Research Council (BMRC). Subject recruitment, sample collection and analyses were funded by the National Medical Research Council (NMRC) COVID-19 Research Fund (COVID19RF-001, COVID19-RF007, COVID190RF-060). The SIgN Immunomonitoring Platform is supported by a BMRC IAF 311006 grant and BMRC transition funds #H16/99/b0/011. The SIgN Flow Cytometry and the Multiple Analyte Platforms were supported by a grant from the National Research Foundation, Immunomonitoring Service Platform ISP) (#NRF2017_SISFP09) and the National Research Foundation Singapore (NRF).
Published: 2021
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18. 24-hour movement behaviour profiles and their transition in children aged 5.5 and 8 years – findings from a prospective cohort study

Author: Falk Müller-Riemenschneider, Claire Goh, Keith M. Godfrey, Yap Seng Chong, Natarajan Padmapriya, Johan G. Eriksson, Shiao-Yng Chan, Lynette Pei-Chi Shek, Bozhi Chen, Jonathan Y. Bernard, Fabian Yap, Yung Seng Lee, Kok Hian Tan, National University of Singapore (NUS), Saw Swee Hock School of Public Health [Singapore, Singapore], Singapore Institute for Clinical Sciences [Singapour] (SICS), Agency for science, technology and research [Singapore] (A*STAR), Khoo Teck Puat – National University Children’s Medical Institute (NUHkids) [Singapore] (KTP-NUCMI), National University Health System [Singapore] (NUHS), KK Women's and Children's Hospital [Singapore], Duke-NUS Medical School [Singapore], Nanyang Technological University [Singapour], University of Southampton, University Hospital Southampton NHS Foundation Trust, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Berlin Institute of Health (BIH), Bernard, Jonathan, Clinicum, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, HUS Helsinki and Uusimaa Hospital District, Lee Kong Chian School of Medicine (LKCMedicine), KK Women’s and Children’s Hospital, and Duke-National University of Singapore
Subjects: CHILDHOOD, Ethnic group, Medicine (miscellaneous), Cohort Studies, PANDAS, Accelerometry, LONGITUDINAL ASSOCIATIONS, EPIDEMIOLOGY, Prospective Studies, Movement Behaviour, Prospective cohort study, Nutritional diseases. Deficiency diseases, Children, Singapore, Nutrition and Dietetics, 1184 Genetics, developmental biology, physiology, TIME, Cohort, SLEEP DURATION, Rabbits, 3143 Nutrition, Public aspects of medicine, RA1-1270, Inactivity, medicine.medical_specialty, RC620-627, Physical activity, Physical Therapy, Sports Therapy and Rehabilitation, Clinical nutrition, DIET, medicine, Animals, Humans, Medicine [Science], OVERWEIGHT, Health consequences, business.industry, Public health, Research, Movement behaviour, Sedentary behaviour, medicine.disease, PHYSICAL-ACTIVITY, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, 3121 General medicine, internal medicine and other clinical medicine, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Sedentary Behavior, business, Sleep, Demography
Abstract: Background Time spent in movement behaviours, including physical activity (PA), sedentary behaviour (SB) and sleep, across the 24-h day may have distinct health consequences. We aimed to describe 24-h movement behaviour (24 h-MB) profiles in children and how profile membership changed from age 5.5 to 8 years. Methods Children in the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort were asked to wear an accelerometer (ActiGraph-GT3X+) on their wrist for seven consecutive days at ages 5.5 and 8 years to measure 24 h-MB patterns. Time spent in night sleep, inactivity (proxy for SB), light PA, moderate PA (MPA), and vigorous PA (VPA) per day were calculated using the R-package GGIR 2.0. Using latent profile analyses (n = 442) we identified 24 h-MB profiles, which were given animal names to convey key characteristics. Latent transition analyses were used to describe the profile membership transition from ages 5.5 to 8 years. Associations with sex and ethnicity were examined. Results We identified four profiles, “Rabbits” (very high-MPA/VPA, low-inactivity and average-night-sleep), “Chimpanzees” (high-MPA, low-inactivity and average-night-sleep), “Pandas” (low-PA, high-inactivity and high-night-sleep) and “Owls” (low-PA, high-inactivity and low-night-sleep), among children at both time points. At ages 5.5 and 8 years, the majority of children were classified into profiles of “Chimpanzees” (51 and 39%, respectively) and “Pandas” (24 and 37%). Half of the sample (49%), particularly “Rabbits”, remained in the same profile at ages 5.5 and 8 years: among children who changed profile the predominant transitions occurred from “Chimpanzees” (27%) and “Owls” (56%) profiles to “Pandas”. Sex, but not ethnicity, was associated with profile membership: compared to girls, boys were more likely to be in the “Rabbits” profile (adjusted OR [95% CI]: 3.6 [1.4, 9.7] and 4.5 [1.8, 10.9] at ages 5.5 and 8 years, respectively) and less likely to be in the “Pandas” profile (0.5 [0.3, 0.9] and 0.4 [0.2, 0.6]) at both ages. Conclusions With increasing age about half the children stayed in the same of four 24 h-MB profiles, while the predominant transition for the remaining children was towards lower PA, higher inactivity and longer sleep duration. These findings can aid development and implementation of public health strategies to promote better health. Study registration This study was registered on 4th August 2010 and is available online at ClinicalTrials.gov: NCT01174875.
Published: 2021
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19. The longitudinal association between early-life screen viewing and abdominal adiposity—findings from a multiethnic birth cohort study

Author: Yung Seng Lee, Suresh Anand Sadananthan, Carla Costa Lança, Seang-Mei Saw, Falk Müller-Riemenschneider, Shirong Cai, Fabian Yap, Mya-Thway Tint, Lynette Pei-Chi Shek, Johan G. Eriksson, Michael S. Kramer, Marielle V. Fortier, Keith M. Godfrey, Yap Seng Chong, Natarajan Padmapriya, Navin Michael, Jia Ying Toh, S. Sendhil Velan, Bozhi Chen, Peter D. Gluckman, Jonathan Y. Bernard, Kok Hian Tan, Mary Foong-Fong Chong, National University of Singapore (NUS), Saw Swee Hock School of Public Health [Singapore, Singapore], Agency for science, technology and research [Singapore] (A*STAR), Singapore Institute for Clinical Sciences [Singapour] (SICS), Singapore Eye Research Institute [Singapore] (SERI), KK Women's and Children's Hospital [Singapore], Duke-National University of Singapore Graduate Medical School, Khoo Teck Puat – National University Children’s Medical Institute (NUHkids) [Singapore] (KTP-NUCMI), National University Health System [Singapore] (NUHS), University of Auckland [Auckland], Duke-NUS Medical School [Singapore], Nanyang Technological University [Singapour], University of Southampton, University Hospital Southampton NHS Foundation Trust, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Yong Loo Lin School of Medicine [Singapore], Folkhälsan Research Center, Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, McGill University = Université McGill [Montréal, Canada], Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Berlin Institute of Health (BIH), and Bernard, Jonathan
Subjects: Male, Pediatric Obesity, medicine.medical_specialty, Screen viewing, Endocrinology, Diabetes and Metabolism, Abdominal Fat, Medicine (miscellaneous), Adipose tissue, 030209 endocrinology & metabolism, Article, Cohort Studies, Screen Time, 03 medical and health sciences, 0302 clinical medicine, Adverse Childhood Experiences, Risk Factors, Internal medicine, Humans, Medicine, 030212 general & internal medicine, Correlation of Data, Singapore, Nutrition and Dietetics, medicine.diagnostic_test, business.industry, Confounding, Magnetic resonance imaging, Magnetic Resonance Imaging, Early life, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Child, Preschool, Female, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Subcutaneous adipose tissue, business, Birth cohort, Cohort study
Abstract: Importance: screen-viewing in adults has been associated with greater abdominal adiposity, with the magnitude of associations varying by sex and ethnicity, but the evidence is lacking at younger ages. We aimed to investigate sex- and ethnic-specific associations of screen-viewing time at ages 2 and 3 years with abdominal adiposity measured by magnetic resonance imaging at age 4.5 years.Methods: The Growing Up in Singapore Towards healthy Outcomes is an ongoing prospective mother-offspring cohort study. Parents/caregivers reported the time their child spent viewing television, handheld devices and computer screens at ages 2 and 3 years. Superficial and deep subcutaneous and visceral abdominal adipose tissue volumes were quantified from magnetic resonance images acquired at age 4.5 years. Associations between screen-viewing time and abdominal adipose tissue volumes were examined by multivariable linear regression adjusting for confounding factors.Results: in the overall sample (n=307), greater total screen-viewing time and handheld device times were associated with higher superficial and deep subcutaneous adipose tissue volumes, but not with visceral adipose tissue volumes. Interactions with child sex were found, with significant associations with superficial and deep subcutaneous and visceral adipose tissue volumes in boys, but not in girls. Among boys, the increases in mean (95% CI) superficial and deep subcutaneous and visceral adipose tissue volumes were 24.3 (9.9, 38.7), 17.6 (7.4, 27.8), and 7.8 (2.1, 13.6) mL per hour increase in daily total screen-viewing time, respectively. Ethnicity-specific analyses showed associations of total screen-viewing time with abdominal adiposity only in Malay children. Television viewing time was not associated with abdominal adiposity.Conclusion: greater total screen-viewing time (and in particular, handheld device viewing time) was associated with higher abdominal adiposity in boys and Malay children. Additional studies are necessary to confirm these associations and to examine screen-viewing interventions for preventing excessive abdominal adiposity and its adverse cardiometabolic consequences.
Published: 2021
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20. Analysis of COVID-19 Incidence and Severity Among Adults Vaccinated With 2-Dose mRNA COVID-19 or Inactivated SARS-CoV-2 Vaccines With and Without Boosters in Singapore

Author: Oon Tek Ng, Kalisvar Marimuthu, Nigel Lim, Ze Qin Lim, Natascha May Thevasagayam, Vanessa Koh, Calvin J. Chiew, Stefan Ma, Mingshi Koh, Pin Yan Low, Say Beng Tan, Joses Ho, Sebastian Maurer-Stroh, Vernon J. M. Lee, Yee-Sin Leo, Kelvin Bryan Tan, Alex R. Cook, Chorh Chuan Tan, Lee Kong Chian School of Medicine (LKCMedicine), National Centre for Infectious Diseases, Singapore, Tan Tock Seng Hospital, Yong Loo Lin School of Medicine, NUS, National University Health System, Singapore, and Saw Swee Hock School of Public Health
Subjects: Male, Singapore, Vaccines, Synthetic, COVID-19 Vaccines, SARS-CoV-2, Messenger RNA, Incidence, COVID-19, Viral Vaccines, General Medicine, Middle Aged, Cohort Studies, Coronavac, Humans, Medicine [Science], Female, RNA, Messenger, mRNA Vaccines, BNT162 Vaccine, Aged
Abstract: ImportanceAssessing booster effectiveness of COVID-19 mRNA vaccine and inactivated SARS-CoV-2 vaccine over longer time intervals and in response to any further SARS-CoV-2 variants is crucial in determining optimal COVID-19 vaccination strategies.ObjectiveTo determine levels of protection against severe COVID-19 and confirmed SARS-CoV-2 infection by types and combinations of vaccine boosters in Singapore during the Omicron wave.Design, Setting, and ParticipantsThis cohort study included Singapore residents aged 30 years or more vaccinated with either at least 2 doses of mRNA COVID-19 vaccines (ie, Pfizer-BioNTech BNT162b2 or Moderna mRNA-1273) or inactivated SARS-CoV-2 vaccines (Sinovac CoronaVac or Sinopharm BBIBP-CorV) as of March 10, 2022. Individuals with a known SARS-CoV-2 infection prior to December 27, 2021, an infection on or before the date of their second vaccine dose, or with reinfection cases were excluded.ExposuresTwo or 3 doses of Pfizer-BioNTech BNT162b2, Moderna mRNA-1273, Sinovac CoronaVac, or Sinopharm BBIBP-CorV.Main Outcomes and MeasuresNotified infections from December 27, 2021, to March 10, 2022, adjusted for age, sex, race, housing status, and calendar days. Estimated booster effectiveness, defined as the relative incidence-rate reduction of severe disease (supplemental oxygen, intensive care, or death) or confirmed infection following 3-dose vaccination compared with 5 months after second mRNA dose, was determined using binomial regression.ResultsAmong 2 441 581 eligible individuals (1 279 047 [52.4%] women, 846 110 (34.7%) aged 60 years and older), there were 319 943 (13.1%) confirmed SARS-CoV-2 infections, of which 1513 (0.4%) were severe COVID-19 cases. mRNA booster effectiveness against confirmed infection 15 to 60 days after boosting was estimated to range from 31.7% to 41.3% for the 4 boosting combinations (homologous BNT162b2, homologous mRNA-1273, 2-dose BNT162b2/mRNA-1273 booster, and 2-dose mRNA-1273/BNT162b2 booster). Five months and more after boosting, estimated booster effectiveness against confirmed infection waned, ranging from –2.8% to 14.6%. Against severe COVID-19, estimated mRNA booster effectiveness was 87.4% (95% CI, 83.3%-90.5%) 15 to 60 days after boosting and 87.2% (95% CI, 84.2%-89.7%) 5 to 6 months after boosting, with no significant difference comparing vaccine combinations. Booster effectiveness against severe COVID-19 15 days to 330 days after 3-dose inactivated COVID-19 vaccination, regardless of combination, was estimated to be 69.6% (95% CI, 48.7%-81.9%).Conclusions and RelevanceBooster mRNA vaccine protection against severe COVID-19 was estimated to be durable over 6 months. Three-dose inactivated SARS-CoV-2 vaccination provided greater protection than 2-dose but weaker protection compared with 3-dose mRNA.
Published: 2022
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21. The longitudinal relationship between early-life screen viewing and 24-hour movement behaviours -findings from a multi-ethnic birth cohort study

Author: Chen, Bozhi, Bernard, Jonathan, Padmapriya, Natarajan, Ning, Yilin, Cai, Shirong, Lança, Carla, Tan, Kok Hian, Yap, Fabian, Chong, Yap-Seng, Shek, Lynette, Godfrey, Keith, Saw, Seang, Chan, Shiao-Yng, Eriksson, Johan, Tan, Chuen, Müller-Riemenschneider, Falk, Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Singapore Institute for Clinical Sciences, Agency for science, technology and research [Singapore] (A*STAR), Yong Loo Lin School of Medicine, National University of Singapore, NUS Graduate School of Integrative Sciences and Engineering [Singapore, Singapore], Singapore Eye Research Institute [Singapore] (SERI), KK Women’s and Children’s Hospital (KKH), Duke-NUS Graduate Medical School, Lee Kong Chian School of Medicine, Nanyang Technological University [Singapour], National University Health System, Medical Research Council, University of Southampton, Folkhälsan Research Center, Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, University of Helsinki, Berlin Institute of Health (BIH), Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Duke-NUS Medical School [Singapore], Nanyang Technological University (NTU), Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, and Bernard, Jonathan
Subjects: [SDV.AEN] Life Sciences [q-bio]/Food and Nutrition, [SDV.MHEP.PED]Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.MHEP.PED] Life Sciences [q-bio]/Human health and pathology/Pediatrics, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.AEN]Life Sciences [q-bio]/Food and Nutrition, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2020
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22. Reflexiones sobre cómo evaluar y mejorar la respuesta a la pandemia de COVID-19

Author: Martín Moreno, José M., Arenas, Alex, Bengoa, Rafael, Borrell, Carme, Franco, Manuel, García-Basteiro, Alberto L., Gestal Otero, Juan Jesús, González López Valcárcel, Beatriz, Hernández Aguado, Ildefonso, Legido-Quigley, Helena, March, Joan Carles, Minué, Sergio, Muntaner, Carles, Vives-Cases, Carmen, Universidad de Alicante. Departamento de Enfermería Comunitaria, Medicina Preventiva y Salud Pública e Historia de la Ciencia, Salud Pública, Investigación en Género (IG), [Martín-Moreno,JM] Departamento de Medicina Preventiva y Salud Pública, Facultad de Medicina e INCLIVA, Universitat de València, Valencia, España. [Arenas,A] Departament d’Enginyeria Informàtica i Matemàtiques, Universitat Rovira i Virgili, Tarragona, España. [Bengoa,R] Instituto de Salud y Estrategia, Bilbao, España. [Borrell,C] Agència de Salut Pública de Barcelona, Barcelona, España. [Borrell,C, Hernández Aguado,I, Vives-Cases,C] CIBER de Epidemiología y Salud Pública (CIBERESP), España. [Franco,M] Grupo de Investigación en Epidemiología y Salud Pública, Facultad de Medicina y Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Madrid, España. [Franco,M] Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland, USA. [García-Basteiro.AL] ISGlobal, Hospital Clínic - Universitat de Barcelona, Barcelona, España. [García-Basteiro.AL] Centro de Investigac¸ ão em Saúde de Manhic¸ a (CISM), Maputo, Mozambique. [Gestal,J] Universidad de Santiago de Compostela, España. [González López-Valcárcel,B] Universidad de Las Palmas de Gran Canaria, España. [Hernández Aguado,I] Universidad Miguel Hernández, Elche, España. [Legido-Quigley,H] London School of Hygiene and Tropical Medicine and Saw Swee Hock School of Public Health, University of Singapore. [March,JC, and Minué,S] Escuela Andaluza de Salud Pública, Granada, España. [Muntaner,C] University of Toronto y Center for Urban Health Solucions, Li Ka Shing Knowledge Institute, Canadá. [Vives-Cases,C] Universidad de Alicante, España.
Subjects: Determinantes sociales de salud, Policy responses, Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans [Medical Subject Headings], Social determinants of health, Respuestas políticas, Prevención y control, Health Care::Environment and Public Health::Public Health [Medical Subject Headings], Health services research, Evaluation, Geographical Locations::Geographic Locations::Europe::Spain [Medical Subject Headings], Health Care::Health Care Economics and Organizations::Organizations::International Agencies::United Nations::World Health Organization [Medical Subject Headings], Health Care::Health Care Facilities, Manpower, and Services::Health Facilities::Hospitals [Medical Subject Headings], Pandemia, Health Care::Health Care Economics and Organizations::Policy::Social Control Policies::Public Policy [Medical Subject Headings], Evaluación, Pandemic, Prevención y control Investigación sobre servicios de salud, Health Care::Environment and Public Health::Public Health::Disease Outbreaks::Epidemics::Pandemics [Medical Subject Headings], COVID-19, Health Care::Health Services Administration::Quality of Health Care::Outcome and Process Assessment (Health Care) [Medical Subject Headings], Diseases::Virus Diseases::RNA Virus Infections::Nidovirales Infections::Coronaviridae Infections::Coronavirus Infections [Medical Subject Headings], Health Care::Health Services Administration::Patient Care Management::Comprehensive Health Care::Primary Health Care [Medical Subject Headings], Investigación sobre servicios de salud, Prevention and control, Medicina Preventiva y Salud Pública, Health Care::Health Care Facilities, Manpower, and Services::Health Services::Community Health Services::Preventive Health Services::Health Education [Medical Subject Headings]
Abstract: La pandemia de COVID-19 ha afectado de manera particularmente intensa a España, pese a su nivel de desarrollo y la elogiada solidez de su Sistema Nacional de Salud. Para comprender qué ha pasado e identificar cómo mejorar la respuesta creemos imprescindible una evaluación independiente multidisciplinaria de la esfera sanitaria, política y socioeconómica. En este trabajo proponemos objetivos, principios, metodología y dimensiones a evaluar, además de esbozar el tipo de resultados y conclusiones esperadas. Nos inspiramos en los requerimientos formulados por el panel independiente de la Organización Mundial de la Salud y en las experiencias evaluativas en otros países, y detallamos la propuesta de aspectos multidimensionales que deben valorarse. La idea es comprender aspectos clave en los ámbitos estudiados y su margen de mejora en lo relativo a preparación, gobernanza, marco normativo, estructuras del Sistema Nacional de Salud (atención primaria, hospitalaria y de salud pública), sector de educación, esquemas de protección social, minimización del impacto económico, y marco y reformas en el ámbito laboral para una sociedad más resiliente. En definitiva, buscamos que este ejercicio sirva no solo para el presente, sino también para que en el futuro estemos mejor preparados y con más ágil capacidad de recuperación ante las amenazas pandémicas que puedan surgir. The COVID-19 pandemic has hit Spain particularly hard, despite being a country with a developed economy and being praised for the robustness of its national health system. In order to understand what happened and to identify how to improve the response, we believe that an independent multi-disciplinary evaluation of the health, political and socio-economic spheres is essential. In this piece we propose objectives, principles, methodology and dimensions to be evaluated, as well as outlining the type of results and conclusions expected. Inspired by the requirements formulated by the WHO Independent Panel for Pandemic Preparedness and Response and by experiences in other countries, we detail the multidimensional aspects to be evaluated. The goal is to understand key aspects in the studied areas and their scope for improvement in terms of preparedness, governance, regulatory framework, national health system structures (primary care, hospital, and public health), education sector, social protection schemes, minimization of economic impact, and labour framework and reforms for a more resilient society. We seek to ensure that this exercise serves not only at present, but also that in the future we are better prepared and more agile in terms of our ability to recover from any pandemic threats that may arise. Ayuda referencia: PI 18/01937 del Fondo de Investigación Sanitaria- Instituto de Salud Carlos III, España, con cofinanciación de Fondos FEDER.
Published: 2020

23. Associations of autozygosity with a broad range of human phenotypes

Author: Dennis O. Mook-Kanamori, Salma M. Wakil, Lisa R. Yanek, Dominique P.V. de Kleijn, Gert J. de Borst, Alison D. Murray, Kamran Guity, Vincent W. V. Jaddoe, Mario Pirastu, Carole Ober, Giuseppe Matullo, Charles N. Rotimi, Daniela Ruggiero, Teresa Tusié-Luna, Wolfgang Lieb, Chew-Kiat Heng, John R. B. Perry, Hortensia Moreno-Macías, Jie Zhou, John M. Starr, Juhani Junttila, Lei Yu, Danielle Posthuma, Marcus Dörr, Yingchang Lu, Jonathan P. Bradfield, Einat Granot-Hershkovitz, Karina Meidtner, Wouter van Rheenen, T Esko, Maris Alver, Wen-Jane Lee, Zhengming Chen, Jennifer A. Brody, Paolo Gasparini, Yii-Der Ida Chen, Cinzia Sala, Peter P. Pramstaller, Gauri Prasad, Nana Matoba, Natalie Terzikhan, Simonetta Guarrera, Bjarke Feenstra, Peter Vollenweider, Smeeta Shrestha, Yi-Jen Hung, Lilja Stefansdottir, David R. Weir, Felix R. Day, Antonietta Robino, Liang Zhang, Lluis Quintana-Murci, Nicholas J. Timpson, Robyn E Wootton, Xue W. Mei, Dharambir K. Sanghera, Gisli Masson, Debbie A Lawlor, Thomas Meitinger, Sharon L.R. Kardia, Peter K. Joshi, Frank J. A. van Rooij, Claude Bouchard, Cassandra N. Spracklen, Ken K. Ong, Taulant Muka, Guanjie Chen, Laura J. Scott, Walter Palmas, Daniel I. Chasman, Sarah E. Medland, Krista Fischer, Blair H. Smith, Jon K. Sigurdsson, Leon Straker, Clara Viberti, Yuan Shi, Louis Pérusse, Peter J. van der Most, Timo Tõnis Sikka, Chris Haley, Kuang Lin, Leif Groop, Hester M. den Ruijter, Hakon Hakonarson, Masato Akiyama, Stephan J. L. Bakker, Sonja I. Berndt, Jeffery R. O'Connell, Cisca Wijmenga, Daniele Cusi, Lorena Orozco, Kristjan H. S. Moore, Kevin Sandow, Stephen S. Rich, Stephanie J. Loomis, George Davey Smith, Cornelia M. van Duijn, Sharvari Rahul Shukla, Agnar Helgason, Thorsten Kessler, Anuj Goel, Dan Mason, David W. Clark, James S. Pankow, Simona Vaccargiu, Uwe Völker, Tamara B. Harris, Matthew A. Allison, Clicerio Gonzalez, Sarju Ralhan, I-Te Lee, Matthias Laudes, Yen-Feng Chiu, Neil Poulter, Benjamin Lehne, John Wright, Lawrence F. Bielak, Philip L. De Jager, Reinhold Schmidt, Ya Xing Wang, Matthias Nauck, Diana L. Cousminer, Patrick Deelen, Ani Manichaikul, Stephen J. Chanock, Anders Hamsten, Barry I. Freedman, Gudmar Thorleifsson, Peter Kraft, Ozren Polasek, Jie Yao, Yoshinori Murakami, Paul M. Ridker, Anubha Mahajan, Struan F.A. Grant, Claudia Schurmann, Bjarni Gunnarsson, Catriona L. K. Barnes, Jessica van Setten, Sandosh Padmanabhan, Alena Stančáková, Markus M. Lerch, Anuradha Jagadeesan, Franco Giulianini, Daniel F. Gudbjartsson, Dwaipayan Bharadwaj, Shengchao Alfred Li, Peter S. Sever, Trevor A. Mori, Albertine J. Oldehinkel, Koichi Matsuda, Xueling Sim, Evangelos Evangelou, André G. Uitterlinden, Pekka Jousilahti, Yukihide Momozawa, Ioanna Tzoulaki, Chao A. Hsiung, Ginevra Biino, Murielle Bochud, Hannele Mattsson, Ilja M. Nolte, Sarah H. Wild, Patricia B. Munroe, Jianjun Liu, Bruce M. Psaty, Giriraj R. Chandak, Masahiro Kanai, Tony R. Merriman, Teemu Palviainen, Rodney A. Lea, Janie Corley, Nicholas J. Wareham, Alan B. Zonderman, Makoto Hirata, Matthew J. Bixley, Caroline Hayward, Nora Franceschini, Kristel R van Eijk, Etienne Patin, Daniel Shriner, Niek Verweij, Xiuqing Guo, Fredrik Karpe, Ruth J. F. Loos, Tiinamaija Tuomi, Ashley van der Spek, Patricia A. Peyser, Jessica D. Faul, Christian Fuchsberger, David Cesarini, Alex S. F. Doney, Janine F. Felix, Cornelius A. Rietveld, Jagadish Vangipurapu, Tanguy Corre, Line Skotte, Rajkumar Dorajoo, Catherine Igartua, Meena Kumari, Nona Sotoodehnia, Leonard H. van den Berg, Najaf Amin, Dale R. Nyholt, Harry Campbell, Massimiliano Cocca, Scott D. Gordon, Patrik K. E. Magnusson, John C. Chambers, Traci M. Bartz, Mike A. Nalls, Tin Aung, Nduna Dzimiri, Colin N. A. Palmer, Rob M. van Dam, Johanna Kuusisto, Russell P. Tracy, Anna Damulina, Pierre-Emmanuel Morange, Sylvain Foisy, Jing Hua Zhao, Nicholas G. Martin, Ching-Yu Cheng, Mariaelisa Graff, Rashmi B. Prasad, Alice Stanton, David-Alexandre Trégouët, Yu Guo, Helen R. Warren, Lyn R. Griffiths, Weihua Meng, Annika Tillander, Christa Meisinger, Albert V. Smith, Mark I. McCarthy, Jingyun Yang, Marine Germain, Neil Small, Linda Broer, Vilmundur Gudnason, Gunnar K. Pálsson, Michele K. Evans, Alexander Teumer, Mark J. Caulfield, Giorgia Girotto, Thomas Lumley, Tinca J. C. Polderman, Wei Zhao, Carlos A. Aguilar-Salinas, Jari Lahti, Matthew L. Albert, Yechiel Friedlander, Veikko Salomaa, Iona Y Millwood, Jan H. Veldink, Archie Campbell, Andres Metspalu, Ulf Gyllensten, Grant W. Montgomery, Veronique Vitart, Jai Rup Singh, Saima Afaq, Alan R. Shuldiner, Miao-Li Chee, Adebowale Adeyemo, Jennifer A. Smith, David A. van Heel, Jaspal S. Kooner, Daniela Toniolo, Cristian Pattaro, Jerome I. Rotter, John Whitfield, Melissa C. Smart, Kari E. North, Salman M. Tajuddin, Tallapragada Divya Sri Priyanka, Christopher A. Haiman, Diane M. Becker, Bernhard K. Krämer, Paul Elliott, Lihua Wang, He Gao, Patrick Sulem, Jinyan Huang, Chiea Chuen Khor, Ruifang Li-Gao, Åsa Johansson, Winfried März, Shai Carmi, Ilaria Gandin, Eric Boerwinkle, Gardar Sveinbjornsson, Saskia P. Hagenaars, Sander W. van der Laan, Gerard Pasterkamp, E-Shyong Tai, Hagit Hochner, Yih Chung Tham, Kent D. Taylor, Kari Stefansson, Matt J. Neville, Craig E. Pennell, Yanchun Bao, Annelot M. Dekker, Helena Schmidt, Mehdi Hedayati, Joshua Elliott, Ian J. Deary, Iris E. Jansen, Judith B. Borja, Edith Hofer, Martin Gögele, Igor Rudan, Lude Franke, Matthias Munz, Folkert W. Asselbergs, Bengt Sennblad, Imo Hofer, John D. Rioux, Pim van der Harst, Bahareh Sedaghati-khayat, Giovanni Cugliari, Morris A. Swertz, Francine Grodstein, Erwin P. Bottinger, Carol A. Wang, Andre Franke, Brian F. Meyer, Adele M. Taylor, Klodian Dhana, Jian'an Luan, Constance Turman, Robert A. Scott, May E. Montasser, Alison Pattie, Marco Brumat, Liming Li, Heiner Boeing, Karen L. Mohlke, Clemens Baumbach, Bishwa Raj Sapkota, Unnur Thorsteinsdottir, Naveed Sattar, Amy R. Bentley, Matthias B. Schulze, Ivana Kolcic, Stella Trompet, Sarah E. Harris, Ayo P. Doumatey, Charumathi Sabanayagam, David Eccles, Mary F. Feitosa, Jost B. Jonas, Massimo Mezzavilla, Mark O. Goodarzi, David Ellinghaus, Heribert Schunkert, Christian Gieger, Heikki V. Huikuri, Lingyao Zeng, Johan G. Eriksson, Woon-Puay Koh, Yucheng Jia, Gurpreet Singh Wander, James F. Wilson, Torgny Karlsson, Steven C. Hunt, Weihua Zhang, Maria Pina Concas, Zoltán Kutalik, Rebecca Rohde, Chittaranjan S. Yajnik, Yasaman Saba, Dabeeru C. Rao, Robin G. Walters, Reedik Mägi, Marie Loh, Eero Vuoksimaa, Josyf C. Mychaleckyj, Katri Räikkönen, Philippe Goyette, M. Arfan Ikram, Alicia Huerta-Chagoya, David J. Porteous, Teresa Nutile, J. Wouter Jukema, Noha A. Yousri, Yoichiro Kamatani, Maryam S. Daneshpour, Babette S. Zemel, Rona J. Strawbridge, Tien Yin Wong, Claudia Langenberg, Amy Moore, Marcus E. Kleber, Fereidoun Azizi, Avner Halevy, Erika Salvi, Francis S. Collins, Markku Laakso, Tim Kacprowski, S. Sunna Ebenesersdóttir, William R. Scott, Michael Boehnke, Jin-Fang Chai, Markus Perola, Nicola Pirastu, Wayne Huey-Herng Sheu, Robert Karlsson, Lenore J. Launer, Lili Milani, Renée de Mutsert, Fernando Rivadeneira, David A. Bennett, Nicola D. Kerrison, Paolo Manunta, Graciela E. Delgado, Magnus Johannesson, Carolina Medina-Gomez, Alanna C. Morrison, Kay-Tee Khaw, Jian-Min Yuan, Jaakko Kaprio, Melanie Waldenberger, Ralf Ewert, Hugoline G. de Haan, Andrew A. Hicks, Yukinori Okada, Maria Sabater-Lleal, Marilyn C. Cornelis, Stephanie J. London, Federica Rizzi, Jeanette Erdmann, Marina Ciullo, Michiaki Kubo, University of Edinburgh, Broad Institute of MIT and Harvard (BROAD INSTITUTE), Harvard Medical School [Boston] (HMS)-Massachusetts Institute of Technology (MIT)-Massachusetts General Hospital [Boston], Osaka University Graduate School of Medicine, Laboratory for Cardiovascular Genomics and Informatics [Yokohama] (RIKEN IMS), RIKEN Center for Integrative Medical Sciences [Yokohama] (RIKEN IMS), RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN)-RIKEN - Institute of Physical and Chemical Research [Japon] (RIKEN), deCODE genetics [Reykjavik], Bradford Institute for Health Research, Bradford Teaching Hospitals NHS Foundation Trust, Bradford, UK (BIHR), Area Science Park, Università degli studi di Trieste = University of Trieste, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Harbor UCLA Medical Center [Torrance, Ca.], Division of Preventive Medicine, Brigham and Women's Hospital, Boston, MA, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Institute of Pop. Genetics, CNR, Sassari, Shardna life science Pula Cagliari, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne = University of Lausanne (UNIL), Medstar Research Institute, Florida State University [Tallahassee] (FSU), University Medical Center [Utrecht], Centre for Population Health Sciences, Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Research Unit on Cardiovascular and Metabolic Diseases (ICAN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), California State University [Sacramento], Department of Thrombosis and Haemostasis, Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Medical University Graz, Department of Neurology, Alzheimer Centre, VU Medical Centre, Amsterdam, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Heidelberg, Frederick National Laboratory for Cancer Research (FNLCR), Wellcome Trust Centre of Human Genetics, University of Oxford, Department of Epidemiology, German Institute of Human Nutrition, University Medical Center Groningen [Groningen] (UMCG), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Department of Medicine, Surgery, and Dentistry, University of Milano, Icelandic Heart Association, Kopavogur, Iceland., Department of Epidemiology [Rotterdam], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Glasgow, Department of Cardiology, Leiden University Medical Center, Leiden, Program in Medical and Population Genetics, The Broad Institute of MIT and Harvard, Cambridge, MA, Queen Mary University of London (QMUL), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Institut de biologie moléculaire des plantes (IBMP), Université de Strasbourg (UNISTRA)-Centre National de la Recherche Scientifique (CNRS), Immunobiologie des Cellules dendritiques, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre de Recherche Translationnelle - Center for Translational Science (CRT), Institut Pasteur [Paris] (IP), Genentech, Inc., Genentech, Inc. [San Francisco], University of Tartu, Duke-NUS Medical School [Singapore], Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Human Genome Sequencing Center, Baylor College of Medicine, Baylor College of Medicine (BCM), Baylor University-Baylor University, University of San Carlos, Office of Population Studies Foundation, Icahn School of Medicine at Mount Sinai [New York] (MSSM), King‘s College London, Division of Cancer Epidemiology and Genetics, National Cancer Institute [Bethesda] (NCI-NIH), National Institutes of Health [Bethesda] (NIH)-National Institutes of Health [Bethesda] (NIH), University of Oxford, Vth Department of Medicine (Nephrology, Hypertensiology, Endocrinology, Diabetology, Rheumatology), Medical Faculty of Mannheim, University of Heidelberg, Division of Molecular & Clinical Medicine, University of Dundee, Ninewells Hospital and Medical School, Dundee, Department of Internal Medicine B, University Medicine Greifswald, Greifswald, University of Chicago, University of Huddersfield, Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Section on Nephrology [Winston-Salem, NC, USA] (Department of Internal Medicine), Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center-Wake Forest Baptist Medical Center, Radcliffe Department of Medicine [Oxford], Harvard School of Public Health, Kunming University of Science and Technology (KMUST), Sans affiliation, University of Southern California (USC), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Centre National de Génotypage (CNG), Commissariat à l'énergie atomique et aux énergies alternatives (CEA), MRC Centrer for Nutritional Epidemiology and Cancer Prevention and Survival, University of Cambridge [UK] (CAM), National University of Singapore (NUS), Experimental Cardiology Laboratory (ECL), Unirversity Medical Center, Department of Medical Statistics, Epidemiology and Medical Informatics, University of Zagreb, Department of Medical Genetics, Department of Medicine, University of Eastern Finland-Kuopio University Hospital, MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, Capital Normal University [Beijing], Saw Swee Hock School of Public Health, National Institute for Environmental Health Sciences Research Triangle Park, Brown University, MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge School of Clinical Medicine, Cambridge, Toyota Research Institute, Helmholtz Zentrum München = German Research Center for Environmental Health, Department of Chemistry and Biochemistry [Boulder], University of Colorado [Boulder], Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Hôpital de la Timone [CHU - APHM] (TIMONE), Metacohorts Consortium, Universiteit Leiden, Institute of Clinical Chemistry and Laboratory Medicine, University of Groningen [Groningen], Medical Research Concil Epidemiology Unit, Institute of Medical Science, Faculty of Medicine, Genetics and Pathology, Imperial College London, Génétique Evolutive Humaine - Human Evolutionary Genetics, Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Brigham and Women's Hospital [Boston], Erasmus University Rotterdam, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System-School of public health, The University of Hong Kong (HKU)-The University of Hong Kong (HKU), Stockholm Bioinformatics Center (SBC), Stockholm University, Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, University of Utrecht, Utrecht, INRH, Department of Genetics, Los Angeles Biomedical Research Institute (LA BioMed), Instituto Nacional de Ciencias Médicas y Nutrición Salvador Zubirán - National Institute of Medical Science and Nutrition Salvador Zubiran [Mexico], Western General Hospital, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Medical Research Council, Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute-University of Pittsburgh Graduate School of Public Health, Zhengzhou University of Light Industry, Department of Electrical and Electronic Engineering [Niigata Univ.], Niigata University, Genetic Epidemiology Unit, University College of London [London] (UCL), Aston Business School, Aston University [Birmingham], Division of Cancer Epidemiology and Genetics [Bethesda, MD, États-Unis], Centre Hospitalier Universitaire Vaudois (CHUV), Pennington Biomedical Research Center, University of Washington [Seattle], Guy's and St Thomas' Hospitals, Northwestern Polytechnical University [Xi'an] (NPU), Department of Social Medicine, University of Bristol [Bristol], Department of Genomics of Common Disease [London, UK], Imperial College London-Hammersmith Hospital NHS Imperial College Healthcare, Department of Internal Medicine, Institute of Clinical Molecular Biology, Kiel University, Medizinische Klinik II, Universität zu Lübeck = University of Lübeck [Lübeck], Clinical and Molecular Epidemiology Unit, Department of Hygiene and Epidemiology, University of Ioannina, Institute for Social Research, University of Michigan System-University of Michigan System, Division of Statistical Genomics, Washington University School of Medicine, Institute for Clinical Molecular Biology, Christian-Albrechts-Universität zu Kiel (CAU), Department of Physics, RISSC-Lab-University of Naples Federico II = Università degli studi di Napoli Federico II, Lund University [Lund], Icelandic Heart Association, Heart Preventive Clinic and Research Institute, The Center for Applied Genomics, Children’s Hospital of Philadelphia (CHOP ), Génétique moléculaire de la neurotransmission et des processus neurodégénératifs (LGMNPN), Université Pierre et Marie Curie - Paris 6 (UPMC)-Centre National de la Recherche Scientifique (CNRS), Medical Research Center Oulu, University of Oulu, University of Utah School of Medicine [Salt Lake City], The Generation R Study, Pediatrics, Epidemiology, Center for Translational and Computational Neuroimmunology [New York, NY, États-Unis] (CTCN), Department of Neurology [New York, NY, États-Unis], Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York]-Columbia University Medical Center (CUMC), Columbia University [New York]-Columbia University [New York], Universität Heidelberg [Heidelberg] = Heidelberg University, Interuniversity Cardiology Institute Netherlands, School of Public Health, University of Michigan [Dearborn], Department of Epidemiology and Public Health, University of Kuopio, Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Institute of Epidemiology and Biobank PopGen, Department of Biostatistics, University of Washington, Universidad Complutense de Madrid = Complutense University of Madrid [Madrid] (UCM), Clinical Institute of Medical and Chemical Laboratory Diagnostics, Karl-Franzens-Universität Graz, Department of Genetics, Biology and Biochemistry, Università degli studi di Torino = University of Turin (UNITO), Oxford Centre for Diabetes, Endocrinology and Metabolism (OCDEM), QIMR Berghofer Medical Research Institute, University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC), University of North Carolina System (UNC)-University of North Carolina System (UNC)-UNC Gillings School of Global Public Health-Carolina Center for Genome Sciences, University of Illinois [Chicago] (UIC), University of Illinois System, Experimental Cardiology Laboratory, Genetic Epidemiology and Clinical Research Group, Umea University Hospital, Functional Genomics, Erasmus Medical Centre, National Human Genome Research Institute (NHGRI), School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Pathological Biochemistry, Royal Infirmary, German Institute of Human Nutrition Potsdam-Rehbrücke (DIfE), Institute of Metabolic Science, MRC, University of Maryland School of Medicine [Baltimore, MD, USA], Centre for Molecular Epidemiology, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, IRCCS San Raffaele Scientific Institute [Milan, Italie], U937, Génomique cardiovasculaire, Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Pierre et Marie Curie - Paris 6 (UPMC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), University of Michigan System, HMNC Brain Health, Singapore Eye Research Institute, Partenaires INRAE, Institut d'Électronique et des Technologies du numéRique (IETR), Université de Nantes (UN)-Université de Rennes (UR)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Psychiatry and Psychotherapy, Rheinische Friedrich-Wilhelms-Universität Bonn, University of Groningen, Department of Genomics of Common Disease, Department of Microbiology, The Freeman Hospital, Department Biostatistics University of North Carolina, Complex Trait Genetics, Amsterdam Neuroscience - Complex Trait Genetics, Clark, D. W., Okada, Y., Moore, K. H. S., Mason, D., Pirastu, N., Gandin, I., Mattsson, H., Barnes, C. L. K., Lin, K., Zhao, J. H., Deelen, P., Rohde, R., Schurmann, C., Guo, X., Giulianini, F., Zhang, W., Medina-Gomez, C., Karlsson, R., Bao, Y., Bartz, T. M., Baumbach, C., Biino, G., Bixley, M. J., Brumat, M., Chai, J. -F., Corre, T., Cousminer, D. L., Dekker, A. M., Eccles, D. A., van Eijk, K. R., Fuchsberger, C., Gao, H., Germain, M., Gordon, S. D., de Haan, H. G., Harris, S. E., Hofer, E., Huerta-Chagoya, A., Igartua, C., Jansen, I. E., Jia, Y., Kacprowski, T., Karlsson, T., Kleber, M. E., Li, S. A., Li-Gao, R., Mahajan, A., Matsuda, K., Meidtner, K., Meng, W., Montasser, M. E., van der Most, P. J., Munz, M., Nutile, T., Palviainen, T., Prasad, G., Prasad, R. B., Priyanka, T. D. S., Rizzi, F., Salvi, E., Sapkota, B. R., Shriner, D., Skotte, L., Smart, M. C., Smith, A. V., van der Spek, A., Spracklen, C. N., Strawbridge, R. J., Tajuddin, S. M., Trompet, S., Turman, C., Verweij, N., Viberti, C., Wang, L., Warren, H. R., Wootton, R. E., Yanek, L. R., Yao, J., Yousri, N. A., Zhao, W., Adeyemo, A. A., Afaq, S., Aguilar-Salinas, C. A., Akiyama, M., Albert, M. L., Allison, M. A., Alver, M., Aung, T., Azizi, F., Bentley, A. R., Boeing, H., Boerwinkle, E., Borja, J. B., de Borst, G. J., Bottinger, E. P., Broer, L., Campbell, H., Chanock, S., Chee, M. -L., Chen, G., Chen, Y. -D. I., Chen, Z., Chiu, Y. -F., Cocca, M., Collins, F. S., Concas, M. P., Corley, J., Cugliari, G., van Dam, R. M., Damulina, A., Daneshpour, M. S., Day, F. R., Delgado, G. E., Dhana, K., Doney, A. S. F., Dorr, M., Doumatey, A. P., Dzimiri, N., Ebenesersdottir, S. S., Elliott, J., Elliott, P., Ewert, R., Felix, J. F., Fischer, K., Freedman, B. I., Girotto, G., Goel, A., Gogele, M., Goodarzi, M. O., Graff, M., Granot-Hershkovitz, E., Grodstein, F., Guarrera, S., Gudbjartsson, D. F., Guity, K., Gunnarsson, B., Guo, Y., Hagenaars, S. P., Haiman, C. A., Halevy, A., Harris, T. B., Hedayati, M., van Heel, D. A., Hirata, M., Hofer, I., Hsiung, C. A., Huang, J., Hung, Y. -J., Ikram, M. A., Jagadeesan, A., Jousilahti, P., Kamatani, Y., Kanai, M., Kerrison, N. D., Kessler, T., Khaw, K. -T., Khor, C. C., de Kleijn, D. P. V., Koh, W. -P., Kolcic, I., Kraft, P., Kramer, B. K., Kutalik, Z., Kuusisto, J., Langenberg, C., Launer, L. J., Lawlor, D. A., Lee, I. -T., Lee, W. -J., Lerch, M. M., Li, L., Liu, J., Loh, M., London, S. J., Loomis, S., Lu, Y., Luan, J., Magi, R., Manichaikul, A. W., Manunta, P., Masson, G., Matoba, N., Mei, X. W., Meisinger, C., Meitinger, T., Mezzavilla, M., Milani, L., Millwood, I. Y., Momozawa, Y., Moore, A., Morange, P. -E., Moreno-Macias, H., Mori, T. A., Morrison, A. C., Muka, T., Murakami, Y., Murray, A. D., de Mutsert, R., Mychaleckyj, J. C., Nalls, M. A., Nauck, M., Neville, M. J., Nolte, I. M., Ong, K. K., Orozco, L., Padmanabhan, S., Palsson, G., Pankow, J. S., Pattaro, C., Pattie, A., Polasek, O., Poulter, N., Pramstaller, P. P., Quintana-Murci, L., Raikkonen, K., Ralhan, S., Rao, D. C., van Rheenen, W., Rich, S. S., Ridker, P. M., Rietveld, C. A., Robino, A., van Rooij, F. J. A., Ruggiero, D., Saba, Y., Sabanayagam, C., Sabater-Lleal, M., Sala, C. F., Salomaa, V., Sandow, K., Schmidt, H., Scott, L. J., Scott, W. R., Sedaghati-Khayat, B., Sennblad, B., van Setten, J., Sever, P. J., Sheu, W. H. -H., Shi, Y., Shrestha, S., Shukla, S. R., Sigurdsson, J. K., Sikka, T. T., Singh, J. R., Smith, B. H., Stancakova, A., Stanton, A., Starr, J. M., Stefansdottir, L., Straker, L., Sulem, P., Sveinbjornsson, G., Swertz, M. A., Taylor, A. M., Taylor, K. D., Terzikhan, N., Tham, Y. -C., Thorleifsson, G., Thorsteinsdottir, U., Tillander, A., Tracy, R. P., Tusie-Luna, T., Tzoulaki, I., Vaccargiu, S., Vangipurapu, J., Veldink, J. H., Vitart, V., Volker, U., Vuoksimaa, E., Wakil, S. M., Waldenberger, M., Wander, G. S., Wang, Y. X., Wareham, N. J., Wild, S., Yajnik, C. S., Yuan, J. -M., Zeng, L., Zhang, L., Zhou, J., Amin, N., Asselbergs, F. W., Bakker, S. J. L., Becker, D. M., Lehne, B., Bennett, D. A., van den Berg, L. H., Berndt, S. I., Bharadwaj, D., Bielak, L. F., Bochud, M., Boehnke, M., Bouchard, C., Bradfield, J. P., Brody, J. A., Campbell, A., Carmi, S., Caulfield, M. J., Cesarini, D., Chambers, J. C., Chandak, G. R., Cheng, C. -Y., Ciullo, M., Cornelis, M., Cusi, D., Smith, G. D., Deary, I. J., Dorajoo, R., van Duijn, C. M., Ellinghaus, D., Erdmann, J., Eriksson, J. G., Evangelou, E., Evans, M. K., Faul, J. D., Feenstra, B., Feitosa, M., Foisy, S., Franke, A., Friedlander, Y., Gasparini, P., Gieger, C., Gonzalez, C., Goyette, P., Grant, S. F. A., Griffiths, L. R., Groop, L., Gudnason, V., Gyllensten, U., Hakonarson, H., Hamsten, A., van der Harst, P., Heng, C. -K., Hicks, A. A., Hochner, H., Huikuri, H., Hunt, S. C., Jaddoe, V. W. V., De Jager, P. L., Johannesson, M., Johansson, A., Jonas, J. B., Jukema, J. W., Junttila, J., Kaprio, J., Kardia, S. L. R., Karpe, F., Kumari, M., Laakso, M., van der Laan, S. W., Lahti, J., Laudes, M., Lea, R. A., Lieb, W., Lumley, T., Martin, N. G., Marz, W., Matullo, G., Mccarthy, M. I., Medland, S. E., Merriman, T. R., Metspalu, A., Meyer, B. F., Mohlke, K. L., Montgomery, G. W., Mook-Kanamori, D., Munroe, P. B., North, K. E., Nyholt, D. R., O'Connell, J. R., Ober, C., Oldehinkel, A. J., Palmas, W., Palmer, C., Pasterkamp, G. G., Patin, E., Pennell, C. E., Perusse, L., Peyser, P. A., Pirastu, M., Polderman, T. J. C., Porteous, D. J., Posthuma, D., Psaty, B. M., Rioux, J. D., Rivadeneira, F., Rotimi, C., Rotter, J. I., Rudan, I., Den Ruijter, H. M., Sanghera, D. K., Sattar, N., Schmidt, R., Schulze, M. B., Schunkert, H., Scott, R. A., Shuldiner, A. R., Sim, X., Small, N., Smith, J. A., Sotoodehnia, N., Tai, E. -S., Teumer, A., Timpson, N. J., Toniolo, D., Tregouet, D. -A., Tuomi, T., Vollenweider, P., Wang, C. A., Weir, D. R., Whitfield, J. B., Wijmenga, C., Wong, T. -Y., Wright, J., Yang, J., Yu, L., Zemel, B. S., Zonderman, A. B., Perola, M., Magnusson, P. K. E., Uitterlinden, A. G., Kooner, J. S., Chasman, D. I., Loos, R. J. F., Franceschini, N., Franke, L., Haley, C. S., Hayward, C., Walters, R. G., Perry, J. R. B., Esko, T., Helgason, A., Stefansson, K., Joshi, P. K., Kubo, M., Wilson, J. F., Læknadeild (HÍ), Faculty of Medicine (UI), Félagsfræði-, mannfræði- og þjóðfræðideild (HÍ), Faculty of Sociology, Anthropology and Folkloristics (UI), Heilbrigðisvísindasvið (HÍ), School of Health Sciences (UI), School of Engineering and Natural Sciences (UI), Verkfræði- og náttúruvísindasvið (HÍ), Félagsvísindasvið (HÍ), School of Social Sciences (UI), Háskóli Íslands, University of Iceland, Clark, David W [0000-0002-1025-9185], Okada, Yukinori [0000-0002-0311-8472], Moore, Kristjan H S [0000-0002-9579-4362], Mason, Dan [0000-0002-0026-9216], Pirastu, Nicola [0000-0002-5363-3886], Gandin, Ilaria [0000-0003-3196-2491], Deelen, Patrick [0000-0002-5654-3966], Schurmann, Claudia [0000-0003-4158-9192], Medina-Gomez, Carolina [0000-0001-7999-5538], Karlsson, Robert [0000-0002-8949-2587], Bao, Yanchun [0000-0002-6102-5098], Biino, Ginevra [0000-0002-9936-946X], Brumat, Marco [0000-0003-3268-039X], Chai, Jin-Fang [0000-0003-3770-1137], Eccles, David A [0000-0003-4634-4995], Gordon, Scott D [0000-0001-7623-328X], Harris, Sarah E [0000-0002-4941-5106], Kacprowski, Tim [0000-0002-5393-2413], Karlsson, Torgny [0000-0001-8095-6149], Kleber, Marcus E [0000-0003-0663-7275], Mahajan, Anubha [0000-0001-5585-3420], Matsuda, Koichi [0000-0001-7292-2686], Meng, Weihua [0000-0001-5388-8494], van der Most, Peter J [0000-0001-8450-3518], Munz, Matthias [0000-0002-4728-3357], Palviainen, Teemu [0000-0002-7847-8384], Prasad, Rashmi B [0000-0002-4400-6741], Salvi, Erika [0000-0002-2724-2291], Skotte, Line [0000-0002-7398-1271], van der Spek, Ashley [0000-0001-7136-0159], Spracklen, Cassandra N [0000-0003-3590-7182], Strawbridge, Rona J [0000-0001-8506-3585], Tajuddin, Salman M [0000-0002-7919-8528], Verweij, Niek [0000-0002-4303-7685], Yanek, Lisa R [0000-0001-7117-1075], Zhao, Wei [0000-0001-7388-0692], Albert, Matthew L [0000-0001-7285-6973], Bentley, Amy R [0000-0002-0827-9101], Chanock, Stephen [0000-0002-2324-3393], Chen, Zhengming [0000-0001-6423-105X], Chiu, Yen-Feng [0000-0002-3352-4500], Cocca, Massimiliano [0000-0002-1127-7596], Collins, Francis S [0000-0002-1023-7410], Cugliari, Giovanni [0000-0002-6080-0718], Damulina, Anna [0000-0001-8241-2727], Day, Felix R [0000-0003-3789-7651], Dhana, Klodian [0000-0002-6397-7009], Dzimiri, Nduna [0000-0003-3395-5754], Elliott, Paul [0000-0002-7511-5684], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Girotto, Giorgia [0000-0003-4507-6589], Goel, Anuj [0000-0003-2307-4021], Goodarzi, Mark O [0000-0001-6364-5103], Gudbjartsson, Daniel F [0000-0002-5222-9857], Guity, Kamran [0000-0002-8379-9668], van Heel, David A [0000-0002-0637-2265], Hirata, Makoto [0000-0002-9994-9958], Ikram, M Arfan [0000-0003-0372-8585], Kamatani, Yoichiro [0000-0001-8748-5597], Kanai, Masahiro [0000-0001-5165-4408], Khor, Chiea Chuen [0000-0002-1128-4729], Kolcic, Ivana [0000-0001-7918-6052], Langenberg, Claudia [0000-0002-5017-7344], Lawlor, Deborah A [0000-0002-6793-2262], Liu, Jianjun [0000-0002-3255-3019], London, Stephanie J [0000-0003-4911-5290], Luan, Jian’an [0000-0003-3137-6337], Matoba, Nana [0000-0001-5329-0134], Mei, Xue W [0000-0002-6279-4884], Mezzavilla, Massimo [0000-0002-9000-4595], Milani, Lili [0000-0002-5323-3102], Mori, Trevor A [0000-0002-5264-9229], Murakami, Yoshinori [0000-0002-2826-4396], Murray, Alison D [0000-0003-4915-4847], Mychaleckyj, Josyf C [0000-0003-2595-0005], Neville, Matt J [0000-0002-6004-5433], Nolte, Ilja M [0000-0001-5047-4077], Ong, Ken K [0000-0003-4689-7530], Pálsson, Gunnar [0000-0002-8231-3961], Pankow, James S [0000-0001-7076-483X], Pattaro, Cristian [0000-0002-4119-0109], Quintana-Murci, Lluis [0000-0003-2429-6320], van Rheenen, Wouter [0000-0002-5860-1533], Rich, Stephen S [0000-0003-3872-7793], Rietveld, Cornelius A [0000-0003-4053-1861], Ruggiero, Daniela [0000-0003-3898-7827], Sabanayagam, Charumathi [0000-0002-4042-4719], Sabater-Lleal, Maria [0000-0002-0128-379X], Sala, Cinzia Felicita [0000-0003-2514-2075], Salomaa, Veikko [0000-0001-7563-5324], Scott, Laura J [0000-0002-4886-5084], Sedaghati-Khayat, Bahareh [0000-0002-7665-8648], Sennblad, Bengt [0000-0002-4360-8003], van Setten, Jessica [0000-0002-4934-7510], Smith, Blair H [0000-0002-5362-9430], Stančáková, Alena [0000-0002-1375-0252], Stanton, Alice [0000-0002-4961-165X], Straker, Leon [0000-0002-7786-4128], Sulem, Patrick [0000-0001-7123-6123], Swertz, Morris A [0000-0002-0979-3401], Taylor, Kent D [0000-0002-2756-4370], Tzoulaki, Ioanna [0000-0002-4275-9328], Veldink, Jan H [0000-0001-5572-9657], Vitart, Veronique [0000-0002-4991-3797], Völker, Uwe [0000-0002-5689-3448], Wander, Gurpreet S [0000-0002-4596-4247], Wang, Ya Xing [0000-0003-2749-7793], Wild, Sarah [0000-0001-7824-2569], Yuan, Jian-Min [0000-0002-4620-3108], Asselbergs, Folkert W [0000-0002-1692-8669], Boehnke, Mike [0000-0002-6442-7754], Bouchard, Claude [0000-0002-0048-491X], Brody, Jennifer A [0000-0001-8509-148X], Campbell, Archie [0000-0003-0198-5078], Caulfield, Mark J [0000-0001-9295-3594], Smith, George Davey [0000-0002-1407-8314], Dorajoo, Rajkumar [0000-0001-6608-2051], Ellinghaus, David [0000-0002-4332-6110], Erdmann, Jeanette [0000-0002-4486-6231], Evangelou, Evangelos [0000-0002-5488-2999], Feenstra, Bjarke [0000-0003-1478-649X], Feitosa, Mary [0000-0002-0933-2410], Franke, Andre [0000-0003-1530-5811], Grant, Struan F A [0000-0003-2025-5302], Griffiths, Lyn R [0000-0002-6774-5475], Groop, Leif [0000-0002-0187-3263], Gudnason, Vilmundur [0000-0001-5696-0084], van der Harst, Pim [0000-0002-2713-686X], Heng, Chew-Kiat [0000-0002-7309-9473], Hicks, Andrew A [0000-0001-6320-0411], Jaddoe, Vincent W V [0000-0003-2939-0041], De Jager, Philip L [0000-0002-8057-2505], Johannesson, Magnus [0000-0001-8759-6393], Johansson, Åsa [0000-0002-2915-4498], Jonas, Jost B [0000-0003-2972-5227], Jukema, J Wouter [0000-0002-3246-8359], Kaprio, Jaakko [0000-0002-3716-2455], Laakso, Markku [0000-0002-3394-7749], van der Laan, Sander W [0000-0001-6888-1404], Lahti, Jari [0000-0002-4310-5297], Martin, Nicholas G [0000-0003-4069-8020], Medland, Sarah E [0000-0003-1382-380X], Merriman, Tony R [0000-0003-0844-8726], Metspalu, Andres [0000-0002-3718-796X], Mohlke, Karen L [0000-0001-6721-153X], Montgomery, Grant W [0000-0002-4140-8139], Munroe, Patricia B [0000-0002-4176-2947], Nyholt, Dale R [0000-0001-7159-3040], Ober, Carole [0000-0003-4626-9809], Oldehinkel, Albertine J [0000-0003-3925-3913], Palmer, Colin [0000-0002-6415-6560], Perusse, Louis [0000-0001-6440-9698], Polderman, Tinca J. C. [0000-0001-5564-301X], Porteous, David J [0000-0003-1249-6106], Rioux, John D [0000-0001-7560-8326], Rivadeneira, Fernando [0000-0001-9435-9441], Rotimi, Charles [0000-0001-5759-053X], Rotter, Jerome I [0000-0001-7191-1723], Rudan, Igor [0000-0001-6993-6884], Sattar, Naveed [0000-0002-1604-2593], Sim, Xueling [0000-0002-1233-7642], Smith, Jennifer A [0000-0002-3575-5468], Teumer, Alexander [0000-0002-8309-094X], Timpson, Nicholas J [0000-0002-7141-9189], Tuomi, Tiinamaija [0000-0002-8306-6202], Wang, Carol A [0000-0002-4301-3974], Weir, David R [0000-0002-1661-2402], Whitfield, John B [0000-0002-1103-0876], Magnusson, Patrik K. E. [0000-0002-7315-7899], Uitterlinden, André G [0000-0002-7276-3387], Loos, Ruth J. F. [0000-0002-8532-5087], Franke, Lude [0000-0002-5159-8802], Haley, Chris S [0000-0002-9811-0210], Hayward, Caroline [0000-0002-9405-9550], Walters, Robin G [0000-0002-9179-0321], Joshi, Peter K [0000-0002-6361-5059], Wilson, James F [0000-0001-5751-9178], Apollo - University of Cambridge Repository, Moore, Kristjan HS [0000-0002-9579-4362], Luan, Jian'an [0000-0003-3137-6337], Grant, Struan FA [0000-0003-2025-5302], Jaddoe, Vincent WV [0000-0003-2939-0041], Polderman, Tinca JC [0000-0001-5564-301X], Magnusson, Patrik KE [0000-0002-7315-7899], Loos, Ruth JF [0000-0002-8532-5087], Neurology, Human genetics, Amsterdam Reproduction & Development (AR&D), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Stem Cell Aging Leukemia and Lymphoma (SALL), Institute for Molecular Medicine Finland, Department of Psychology and Logopedics, University Management, Developmental Psychology Research Group, Staff Services, Cognitive and Brain Aging, Research Programs Unit, Diabetes and Obesity Research Program, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Clinicum, University of Helsinki, Centre of Excellence in Complex Disease Genetics, Department of Public Health, Genetic Epidemiology, Helsinki Collegium for Advanced Studies, HUS Abdominal Center, Endokrinologian yksikkö, Bradford Teaching Hospitals NHS Foundation Trust [Bradford, UK] (BTHFT), University of Trieste, Université de Lausanne (UNIL), Unité de Recherche sur les Maladies Cardiovasculaires, du Métabolisme et de la Nutrition = Institute of cardiometabolism and nutrition (ICAN), Consiglio Nazionale delle Ricerche (CNR), Centre National de la Recherche Scientifique (CNRS)-Université de Strasbourg (UNISTRA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Institut Pasteur [Paris], University of Oxford [Oxford], Medical Genetics, Dept. RSD and Public Health, IRCCS-Burlo Garofolo/University of Trieste, sans affiliation, Helmholtz-Zentrum München (HZM), Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Institute of Cardiovascular Science, University College London, Hammersmith Hospital NHS Imperial College Healthcare-Imperial College London, Universität zu Lübeck [Lübeck], University of Ioannina Medical School, Università degli studi di Napoli Federico II-RISSC-Lab, Universität Heidelberg [Heidelberg], University of Turin, University of California-University of California, Nantes Université (NU)-Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées - Rennes (INSA Rennes), Institut National des Sciences Appliquées (INSA)-Université de Rennes (UNIV-RENNES)-Institut National des Sciences Appliquées (INSA)-CentraleSupélec-Centre National de la Recherche Scientifique (CNRS), University of Helsinki-University of Helsinki, Université de Nantes (UN)-Université de Rennes 1 (UR1), Erasmus MC other, Internal Medicine, and Applied Economics
Subjects: 0301 basic medicine, 631/208/1397, Chemistry(all), Health Status, [SDV]Life Sciences [q-bio], LOCI, General Physics and Astronomy, MESH: Haplotype, MESH: Cognition, 030105 genetics & heredity, Runs of Homozygosity, Biochemistry, Consanguinity, Cognition, Inbreeding depression, 2.1 Biological and endogenous factors, Body Size, Inbreeding, Skyldleikarækt, Aetiology, Human phenotypes, lcsh:Science, MESH: Health Status, Genetics, Multidisciplinary, Inbreeding Depression, Confounding, Homozygote, RUNS, 631/208/205, 631/208/721, 3. Good health, genomic inbreeding coefficients, MESH: Risk-Taking, 631/208/730, Autozygosit, homozygosity, Erfðarannsóknir, Medical Genetics, genomic inbreeding coefficient, MESH: Homozygote, Offspring, Science, Autozygosity, Blóðsifjar, 610 Medicine & health, Biology, INBREEDING DEPRESSION, HOMOZYGOSITY, FERTILITY, QUANTIFICATION, Physics and Astronomy(all), General Biochemistry, Genetics and Molecular Biology, Article, Association, 03 medical and health sciences, Risk-Taking, 360 Social problems & social services, Journal Article, Humans, ddc:610, Allele, Alleles, Medicinsk genetik, Genetic association study, MESH: Consanguinity, MESH: Body Size, MESH: Humans, Biochemistry, Genetics and Molecular Biology(all), MESH: Alleles, Haplotype, MESH: Fertility, General Chemistry, Brain Disorders, MESH: Inbreeding Depression, 030104 developmental biology, Fertility, Haplotypes, Genetic markers, lcsh:Q, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, 3111 Biomedicine, Genetics and Molecular Biology(all)
Abstract: Publisher's version (útgefin grein)., In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p < 0.0005) with apparently deleterious changes in 32 out of 100 traits analysed. These changes are associated with runs of homozygosity (ROH), but not with common variant homozygosity, suggesting that genetic variants associated with inbreeding depression are predominantly rare. The effect on fertility is striking: FROH equivalent to the offspring of first cousins is associated with a 55% decrease [95% CI 44–66%] in the odds of having children. Finally, the effects of FROH are confirmed within full-sibling pairs, where the variation in FROH is independent of all environmental confounding., This paper is the work of the ROHgen consortium. We thank the Sigma T2D Consortium, whose members are detailed in Supplementary Note 3. We thank the UK Biobank Resource, approved under application 19655; we acknowledge funding from the UK Medical Research Council Human Genetics Unit and MRC Doctoral Training Programme in Precision Medicine. We also thank Neil Robertson, Wellcome Trust Centre for Human Genetics, Oxford, for use of his author details management software, Authorial. Finally, we thank all the participants, researchers and funders of ROHgen cohorts. Cohort-specific acknowledgements are in Supplementary Data 2; personal acknowledgements and disclosures are in Supplementary Note 2. We thank Rachel Edwards for administrative assistance.
Published: 2019
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24. Antibody Treatment against Angiopoietin-Like 4 Reduces Pulmonary Edema and Injury in Secondary Pneumococcal Pneumonia

Author: Koichi Izumikawa, Vincent T. K. Chow, Ka Wai Kwok, Jean-Pierre Quenot, Noriho Sakamoto, Nguan Soon Tan, Liang Li, Wooi Keong Teh, Benjamin Jie Wei Foo, Stéphane Mandard, Laurent Lagrost, Hiroshi Mukae, Ju Ee Seet, Pengcheng Zhu, Fang He, Gurjeet S. Kohli, Liang Yang, Hyungwon Choi, Martin L. Buist, Institute of Biomedicine and Biotechnology [Shenzhen, China], Institut Pasteur de Shanghai, Académie des Sciences de Chine - Chinese Academy of Sciences (IPS-CAS), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Shenzhen Institutes of Advanced Technology [Shenzhen, China], School of Biological Sciences [Singapore, Singapore], Nanyang Technological University [Singapour], Department of Respiratory Medicine [Nagasaki, Japan] (Unit of Translational Medicine), Nagasaki University Graduate School of Biomedical Sciences [Japan], Lipides - Nutrition - Cancer [Dijon - U1231] (LNC), Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Excellence : Lipoprotéines et Santé : prévention et Traitement des maladies Inflammatoires et du Cancer (LabEx LipSTIC), Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université de Montpellier (UM), CHU Dijon, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Singapore Centre for Environmental Life Sciences Engineering [Singapore] (SCELSE), Saw Swee Hock School of Public Health [Singapore, Singapore], National University of Singapore (NUS), Department of Biomedical Engineering [Singapore], Department of Pathology [Singapour], School of Medicine [Shenzhen, China], Southern University of Science and Technology of China (SUSTech), Zhejiang Provincial Key Laboratory of Preventive Veterinary Medicine [Hangzhou, China], Huzhou University [Zhejiang]-Institute of Preventive Veterinary Medicine [Hangzhou, China]-College of Animal Sciences [Hangzhou, China], Host and Pathogen Interactivity Laboratory [Singapore, Singapore] (Department of Microbiology and Immunology), National University of Singapore (NUS)-Yong Loo Lin School of Medicine [Singapore], Lee Kong Chian School of Medicine, Nanyang Technological University (NTU), Cooperative Basic Research Grant NMRC/CBRG/ 0030/2013 and National Health Innovation Centre Grant NHIC-I2D-1509081 from the National Medical Research Council, SingaporeNational Natural Science Foundation of China (81771617)French National Research Agency (ANR-11-LABX-0021-01-LipSTIC LabEx)Start-Up Grant Y01416206 from Southern University of Science and Technology (China), ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011), Pirofski, Liise-anne, Lee Kong Chian School of Medicine (LKCMedicine), School of Biological Sciences, Interdisciplinary Graduate School (IGS), Singapore Centre for Environmental Life Sciences and Engineering, Université de Bourgogne (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer Georges-François Leclerc [Dijon] (UNICANCER/CRLCC-CGFL), UNICANCER-UNICANCER-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-Université de Montpellier (UM)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-Franche-Comté] (EFS [Bourgogne-Franche-Comté])-Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Southern University of Science and Technology (SUSTech), ANR-11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer(2011), Mandard, Stéphane, Laboratoires d'excellence - Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du cancer - - Lipstic2011 - ANR-11-LABX-0021 - LABX - VALID, Institut National de la Recherche Agronomique (INRA)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Paris-Sud - Paris 11 (UP11)-École pratique des hautes études (EPHE)-Institut Gustave Roussy (IGR)-Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)-Université de Bourgogne (UB)-Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon)-Centre Régional de Lutte contre le cancer - Centre Georges-François Leclerc (CRLCC - CGFL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Fédération Francophone de la Cancérologie Digestive, FFCD-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Etablissement français du sang [Bourgogne-France-Comté] (EFS [Bourgogne-France-Comté])-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon)-Université de Franche-Comté (UFC)-Université de Montpellier (UM), Unité de soins intensifs [CHU Dijon], Singapore Centre for Environmental Life Sciences Engineering [Singapore, Singapore] (SCELSE), Nanyang Technological University [Singapour]-Interdisciplinary Graduate School [Singapore, Singapore], National University of Singapore (NUS)-Yong Loo Lin School of Medicine, Lee Kong Chian School of Medicine [Singapore, Singapore], and ANR: 11-LABX-0021,Lipstic,Lipoprotéines et santé : prévention et traitement des maladies inflammatoires non vasculaires et du(2011)
Subjects: antibiotic resistance, Antibiotics, medicine.disease_cause, Mice, 0302 clinical medicine, ANGPTL4, Medicine, Lung, Mice, Inbred BALB C, 0303 health sciences, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Coinfection, Biological sciences [Science], Pulmonary edema, QR1-502, Anti-Bacterial Agents, 3. Good health, Streptococcus pneumoniae, [SDV.MP]Life Sciences [q-bio]/Microbiology and Parasitology, 030220 oncology & carcinogenesis, Pneumococcal pneumonia, Female, Research Article, medicine.drug_class, Secondary infection, Secondary Bacterial Pneumonia, Pulmonary Edema, host-directed immunotherapeutics, Lung injury, Microbiology, Antibodies, Host-Microbe Biology, 03 medical and health sciences, Immune system, Antibiotic resistance, Virology, [SDV.BBM] Life Sciences [q-bio]/Biochemistry, Molecular Biology, Angiopoietin-Like Protein 4, Animals, [SDV.BBM]Life Sciences [q-bio]/Biochemistry, Molecular Biology, [SDV.MP] Life Sciences [q-bio]/Microbiology and Parasitology, vascular permeability, 030304 developmental biology, secondary bacterial pneumonia, Inflammation, business.industry, Pneumonia, Pneumococcal, medicine.disease, Disease Models, Animal, Immunology, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Despite extensive global efforts, secondary bacterial pneumonia still represents a major cause of death in developing countries and is an important cause of long-term functional disability arising from lung tissue damage. Newer approaches to improving treatment outcomes are needed to reduce the significant morbidity and mortality caused by infectious diseases. Our study, using an experimental mouse model of secondary S. pneumoniae infection, shows that a multimodal treatment that concurrently targets host and pathogen factors improved lung tissue integrity and extended the median survival time of infected mice. The immunoneutralization of host protein cANGPTL4 reduced the severity of pulmonary edema and damage. We show that host-directed therapeutic strategies as well as neutralizing antibodies against pathogen virulence factors are viable adjuncts to standard antimicrobial treatments such as antibiotics. In view of their different modes of action compared to antibiotics, concurrent immunotherapies using antibodies are potentially efficacious against secondary pneumococcal pneumonia caused by antibiotic-resistant pathogens., Secondary bacterial lung infection by Streptococcus pneumoniae (S. pneumoniae) poses a serious health concern, especially in developing countries. We posit that the emergence of multiantibiotic-resistant strains will jeopardize current treatments in these regions. Deaths arising from secondary infections are more often associated with acute lung injury, a common consequence of hypercytokinemia, than with the infection per se. Given that secondary bacterial pneumonia often has a poor prognosis, newer approaches to improve treatment outcomes are urgently needed to reduce the high levels of morbidity and mortality. Using a sequential dual-infection mouse model of secondary bacterial lung infection, we show that host-directed therapy via immunoneutralization of the angiopoietin-like 4 c-isoform (cANGPTL4) reduced pulmonary edema and damage in infected mice. RNA sequencing analysis revealed that anti-cANGPTL4 treatment improved immune and coagulation functions and reduced internal bleeding and edema. Importantly, anti-cANGPTL4 antibody, when used concurrently with either conventional antibiotics or antipneumolysin antibody, prolonged the median survival of mice compared to monotherapy. Anti-cANGPTL4 treatment enhanced immune cell phagocytosis of bacteria while restricting excessive inflammation. This modification of immune responses improved the disease outcomes of secondary pneumococcal pneumonia. Taken together, our study emphasizes that host-directed therapeutic strategies are viable adjuncts to standard antimicrobial treatments.
Published: 2019
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25. GenomegaMap: within-species genome-widedN/dSestimation from over 10,000 genomes

Author: Wilson, DJ, Crook, DW, Peto, TEA, Walker, AS, Hoosdally, SJ, Gibertoni Cruz, AL, Carter, J, Grazian, C, Earle, SG, Kouchaki, S, Lachapelle, A, Yang, Y, Clifton, DA, Fowler, PW, Iqbal, Z, Hunt, M, Knaggs, J, Smith, EG, Rathod, P, Jarrett, L, Matias, D, Cirillo, DM, Borroni, E, Battaglia, S, Ghodousi, A, Spitaleri, A, Cabibbe, A, Tahseen, S, Nilgiriwala, K, Shah, S, Rodrigues, C, Kambli, P, Surve, U, Khot, R, Niemann, S, Kohl, TA, Merker, M, Hoffmann, H, Todt, K, Plesnik, S, Ismail, N, Omar, SV, Joseph, L, Thwaites, G, Thuong, TNT, Ngoc, NH, Srinivasan, V, Walker, TM, Moore, D, Coronel, J, Solano, W, Gao, GF, He, G, Zhao, Y, Liu, C, Ma, A, Zhu, B, Laurenson, I, Claxton, P, Koch, A, Wilkinson, R, Lalvani, A, Posey, J, Gardy, J, Werngren, J, Paton, N, Jou, R, Wu, M-H, Lin, W-H, Ferrazoli, L, De Oliveira, RS, Arandjelovic, I, Chaiprasert, A, Comas, I, Roig, CJ, Drobniewski, FA, Farhat, MR, Gao, Q, Hee, ROT, Sintchenko, V, Supply, P, Van Soolingen, D, University of Oxford, Centre d’Infection et d’Immunité de Lille - INSERM U 1019 - UMR 9017 - UMR 8204 (CIIL), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Centre National de la Recherche Scientifique (CNRS), D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre., Members of the CRyPTIC Consortium : Derrick W. Crook, Timothy E.A. Peto, A. Sarah Walker, Sarah J. Hoosdally, Ana L. Gibertoni Cruz, Joshua Carter, Clara Grazian, Sarah G. Earle, Samaneh Kouchaki, Alexander Lachapelle, Yang Yang, David A. Clifton, and Philip W. Fowler, University of Oxford, Zamin Iqbal, Martin Hunt, and Jeffrey Knaggs, European Bioinformatics Institute, E. Grace Smith, Priti Rathod, Lisa Jarrett, and Daniela Matias, Public Health England, Birmingham, Daniela M. Cirillo, Emanuele Borroni, Simone Battaglia, Arash Ghodousi, Andrea Spitaleri, and Andrea Cabibbe, Emerging Bacterial Pathogens Unit, IRCCS San Raffaele Scientific Institute, Milan, Sabira Tahseen, National Tuberculosis Control Program Pakistan, Islamabad, Kayzad Nilgiriwala and Sanchi Shah, The Foundation for Medical Research, Mumbai, Camilla Rodrigues, Priti Kambli, Utkarsha Surve, and Rukhsar Khot, P.D. Hinduja National Hospital and Medical Research Centre, Mumbai, Stefan Niemann, Thomas A. Kohl, and Matthias Merker, Research Center Borstel, Harald Hoffmann, Katharina Todt, and Sara Plesnik, Institute of Microbiology & Laboratory Medicine, IML Red, Gauting, Nazir Ismail, Shaheed Vally Omar, and Lavania Joseph, National Institute for Communicable Diseases, Johannesburg, Guy Thwaites, Thuong Nguyen Thuy Thuong, Nhung Hoang Ngoc, Vijay Srinivasan, and Timothy M. Walker, Oxford University Clinical Research Unit, Ho Chi Minh City, David Moore, Jorge Coronel and Walter Solano, London School of Hygiene and Tropical Medicine and Universidad Peruana Cayetano Heredá, Lima, George F. Gao, Guangxue He, Yanlin Zhao, and Chunfa Liu, China CDC, Beijing, Aijing Ma, Shenzhen Third People’s Hospital, Shenzhen, Baoli Zhu, Institute of Microbiology, CAS, Beijing, Ian Laurenson and Pauline Claxton, Scottish Mycobacteria Reference Laboratory, Edinburgh, Anastasia Koch, Robert Wilkinson, University of Cape Town, Ajit Lalvani, Imperial College London, James Posey, CDC Atlanta, Jennifer Gardy, University of British Columbia, Jim Werngren, Public Health Agency of Sweden, Nicholas Paton, National University of Singapore, Ruwen Jou, Mei-Hua Wu, Wan-Hsuan Lin, CDC Taiwan, Lucilaine Ferrazoli, Rosangela Siqueira de Oliveira, Institute Adolfo Lutz, São Paulo. Authors contributing to the CRyPTIC Consortium are (in alphabetical order): Irena Arandjelovic (Institute of Microbiology and Immunology, Faculty of Medicine, University of Belgrade, Belgrade, Serbia), Angkana Chaiprasert (Faculty of Medicine Siriraj Hospital, Mahidol University, Thailand), Iñaki Comas (Instituto de Biomedicina de Valencia [IBV-CSIC], Calle Jaime Roig, Valencia, Spain, FISABIO Public Health, Valencia, Spain, CIBER in Epidemiology and Public Health, Madrid, Spain), Francis A. Drobniewski (Imperial College, London, UK), Maha R. Farhat (Harvard Medical School, Boston, USA), Qian Gao (Shanghai Medical College, Fudan University, Shanghai, China), Rick Ong Twee Hee (Saw Swee Hock School of Public Health, National University of Singapore, Singapore), Vitali Sintchenko (Centre for Infectious Diseases and Microbiology—Public Health, University of Sydney, Sydney, Australia), Philip Supply (Univ. Lille, CNRS, Inserm, CHU Lille, Institut Pasteur de Lille, U1019—UMR 8204—CIIL—Centre d’Infection et d’Immunité de Lille, F-59000 Lille, France), and Dick van Soolingen (National Institute for Public Health and the Environment [RIVM], Bilthoven, The Netherlands)., Supply, Philip, Consortium, CRyPTIC, University of Oxford [Oxford], Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)-Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Royal Society (UK), Bill & Melinda Gates Foundation, Newton Fund, Comas, Iñaki [0000-0001-5504-9408], and Comas, Iñaki
Subjects: Natural selection, [SDV]Life Sciences [q-bio], Population genetics, adaptation, Computational biology, Biology, AcademicSubjects/SCI01180, 0601 Biochemistry and Cell Biology, Genome, Coalescent theory, DEAD-box RNA Helicases, Big data, 03 medical and health sciences, 0603 Evolutionary Biology, big data, Parent-dependent mutation, Genetics, dN/dS, Adaptation, Selection, Genetic, Molecular Biology, Allele frequency, Ecology, Evolution, Behavior and Systematics, Silent Mutation, Selection (genetic algorithm), 030304 developmental biology, Evolutionary Biology, 0604 Genetics, 0303 health sciences, Models, Genetic, Phylogenetic tree, 030306 microbiology, AcademicSubjects/SCI01130, natural selection, Mycobacterium tuberculosis, Recombination, Resources, recombination, 3. Good health, [SDV] Life Sciences [q-bio], Genetic Techniques, Mutation (genetic algorithm), parent-dependent mutation, Genome, Bacterial
Abstract: 11 págs, 4 figuras y fórmulas matemáticas. Material suplementario en: http://dx.doi.org/10.1093/molbev/msaa069, The dN/dS ratio provides evidence of adaptation or functional constraint in protein-coding genes by quantifying the relative excess or deficit of amino acid-replacing versus silent nucleotide variation. Inexpensive sequencing promises a better understanding of parameters, such as dN/dS, but analyzing very large data sets poses a major statistical challenge. Here, I introduce genomegaMap for estimating within-species genome-wide variation in dN/dS, and I apply it to 3,979 genes across 10,209 tuberculosis genomes to characterize the selection pressures shaping this global pathogen. GenomegaMap is a phylogeny-free method that addresses two major problems with existing approaches: 1) It is fast no matter how large the sample size and 2) it is robust to recombination, which causes phylogenetic methods to report artefactual signals of adaptation. GenomegaMap uses population genetics theory to approximate the distribution of allele frequencies under general, parent-dependent mutation models. Coalescent simulations show that substitution parameters are well estimated even when genomegaMap's simplifying assumption of independence among sites is violated. I demonstrate the ability of genomegaMap to detect genuine signatures of selection at antimicrobial resistance-conferring substitutions in Mycobacterium tuberculosis and describe a novel signature of selection in the cold-shock DEAD-box protein A gene deaD/csdA. The genomegaMap approach helps accelerate the exploitation of big data for gaining new insights into evolution within species., D.J.W. is a Sir Henry Dale Fellow, jointly funded by the Wellcome Trust and the Royal Society (grant no. 101237/Z/13/B) and is a Big Data Institute Robertson Fellow. The CRyPTIC Consortium was supported by grants from the Bill and Melinda Gates Foundation (OPP1133541) and a Wellcome Trust/Newton Fund-MRC Collaborative Award (200205/Z/15/Z). F.A.D. was supported by the Imperial Biomedical Research Centre
Published: 2019
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26. Maternal Lutein and Zeaxanthin Concentrations in Relation to Offspring Visual Acuity at 3 Years of Age: The GUSTO Study

Author: Jun Shi Lai, Mary Foong-Fong Chong, Vaishnavi O Veetil, Lynette Pei-Chi Shek, Choon Nam Ong, Seang-Mei Saw, Cheryl Ngo, Keith M. Godfrey, Carla Costa Lança, Fabian Yap, Bee Lan Lee, Yap Seng Chong, Peter D. Gluckman, Kok Hian Tan, Lee Kong Chian School of Medicine (LKCMedicine), Duke-NUS Graduate Medical School, Saw Swee Hock School of Public Health, and Singapore Eye Research Institute
Subjects: Male, Lutein, Visual acuity, genetic structures, visual acuity, Physiology, chemistry.chemical_compound, 0302 clinical medicine, Outcome Assessment, Health Care, Medicine, 10. No inequality, Singapore, child, Nutrition and Dietetics, Confounding, food and beverages, Zeaxanthin, zeaxanthin, Child, Preschool, Prenatal Exposure Delayed Effects, Cohort, symbols, Female, pregnancy, medicine.symptom, lcsh:Nutrition. Foods and food supply, Adult, endocrine system, Offspring, Vision Disorders, lcsh:TX341-641, Article, 03 medical and health sciences, symbols.namesake, Zeaxanthins, Humans, Medicine [Science], Poisson regression, lutein, Pregnancy, business.industry, Maternal Nutritional Physiological Phenomena, medicine.disease, eye diseases, Pregnancy Complications, chemistry, 030221 ophthalmology & optometry, sense organs, business, Maternal Serum Screening Tests, 030217 neurology & neurosurgery, Food Science
Abstract: Lutein and zeaxanthin play important roles in visual functions, but their influence on early visual development is unclear. We related maternal lutein and zeaxanthin concentrations during pregnancy to offspring visual acuity (VA) in 471 mother&ndash, child pairs from the Growing Up in Singapore Towards healthy Outcomes (GUSTO) cohort. Maternal concentrations of plasma lutein and zeaxanthin were determined at delivery. We measured uncorrected distance of VA in 3-year old children using a LEA Symbols chart, readings were converted to the logarithm of Minimum Angle of Resolution (logMAR), with &gt, 0.3 logMAR indicating poor VA. Associations were examined using linear or Poisson regression adjusted for confounders. The median (inter-quartile range) of maternal lutein and zeaxanthin concentrations were 0.13 (0.09, 0.18) and 0.09 (0.07, 0.12) &micro, mol/L, respectively. A total of 126 children had poor VA. The highest tertile of maternal zeaxanthin concentration was associated with 38% lower likelihood of poor VA in children (95% CI: 0.42, 0.93, p-Trends = 0.02). Higher maternal lutein concentrations were associated with a lower likelihood of poor VA in children (RR 0.60 (95% CI: 0.40, 0.88) for middle tertile, RR 0.78 (95% CI: 0.51, 1.19) for highest tertile (p-Quadratic = 0.02)). In conclusion, lutein and zeaxanthin status during pregnancy may influence offspring early visual development, but the results require confirmation with further studies, including more comprehensive measurements of macular functions.
Published: 2020
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27. Body mass index and lung cancer risk: a pooled analysis based on nested case-control studies from four cohort studies

Author: Gary E. Goodman, Lesley M. Butler, Paolo Vineis, Woon-Puay Koh, Mattias Johansson, Isabelle Stücker, Harinakshi Sanikini, Jian-Min Yuan, Chu Chen, Annika Steffen, Rayjean J. Hung, Matt J. Barnett, Yu-Tang Gao, Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Division of Cancer Control and Population Sciences, University of Pittsburgh Cancer Institute, Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), Duke-NUS Medical School [Singapore], Saw Swee Hock School of Public Health, National University of Singapore (NUS), Department of Epidemiology, Shanghai Cancer Institute, School of Medicine [Shanghai Jiaotong University], Shanghai Jiaotong University, Deutsches Institut für Ernährungsforschung Potsdam-Rehbrücke (DifE), Leibniz Association, Centre International de Recherche contre le Cancer - International Agency for Research on Cancer (CIRC - IARC), Organisation Mondiale de la Santé / World Health Organization Office (OMS / WHO), Department of Epidemiology and Biostatistics [Imperial College London], Imperial College London, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center [Seattle] (FHCRC), Lunenfeld-Tanenbaum Research Institute [Toronto, Canada], This work was supported by the Fondation de France and Ecole doctarale de Sante Publique (ED420). The EPIC study has been supported by the Europe Against Cancer Program of the European Commission. The SCHS and SCS were supported by NCI, NIH grants U01-CA63673, UM1-CA167462 and R01-CA111703. The CARET was supported by the National Institute of Health (U01 CA63673) and the Fred Hutchinson Cancer Research Center, Seattle, WA., BMC, BMC, and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Cancer Research, Lung Neoplasms, [SDV]Life Sciences [q-bio], Overweight, Body Mass Index, 0302 clinical medicine, Risk Factors, 030212 general & internal medicine, 2. Zero hunger, Smoking, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], Oncology, 030220 oncology & carcinogenesis, MENDELIAN RANDOMIZATION, Female, Lung cancer, medicine.symptom, Underweight, Life Sciences & Biomedicine, Research Article, Cohort study, Adult, medicine.medical_specialty, HYPOXIA-INDUCIBLE FACTOR, [SDV.CAN]Life Sciences [q-bio]/Cancer, SECULAR TRENDS, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Genetics, medicine, Humans, Oncology & Carcinogenesis, Obesity, METAANALYSIS, Aged, Science & Technology, HISTOLOGIC TYPE, business.industry, MORTALITY, Case-control study, Odds ratio, medicine.disease, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, Case-Control Studies, Nested case-control study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, WEIGHT, SINGAPORE CHINESE HEALTH, business, 1112 Oncology And Carcinogenesis, Body mass index
Abstract: Background Obesity has been proposed as a potential protective factor against lung cancer. We examined the association between BMI and lung cancer risk in a pooled analysis based on nested case-control studies from four cohort studies. Methods A case-control study was nested within four cohorts in USA, Europe, China and Singapore that included 4172 cases and 8471 control subjects. BMI at baseline was calculated as weight in kilograms divided by height in meters squared (kg/m2), and classified into 4 categories: underweight (BMI
Published: 2018
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28. Introducing Health Impact Assessment

Author: Jabot, Françoise, Centre de Recherches sur l'Action Politique en Europe (ARENES), Université de Rennes (UR)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), École des Hautes Études en Santé Publique [EHESP] (EHESP), Département des sciences humaines et sociales (SHS), NUS Saw Swee Hock School of Public Health (SSHSPH), EHESP French National School of Public Health / Ecole des hutes études en santé publique, Université de Rennes 1 (UR1), Université de Rennes (UNIV-RENNES)-Université de Rennes (UNIV-RENNES)-Institut d'Études Politiques [IEP] - Rennes-École des Hautes Études en Santé Publique [EHESP] (EHESP)-Centre National de la Recherche Scientifique (CNRS), and EHESP, SCD
Subjects: [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [SHS] Humanities and Social Sciences, Health Impact Assessment, ComputingMilieux_MISCELLANEOUS, [SHS]Humanities and Social Sciences
Abstract: International audience
Published: 2016

29. Functional mechanisms underlying pleiotropic risk alleles at the 19p13.1 breast-ovarian cancer susceptibility locus

Author: Lawrenson, Kate, Kar, Siddhartha, McCue, Karen, Kuchenbaeker, Karoline, Michailidou, Kyriaki, Tyrer, Jonathan, Beesley, Jonathan, Ramus, Susan J., Li, Qiyuan, Delgado, Melissa K., Lee, Janet M., Aittomäki, Kristiina, Andrulis, Irene L., Anton-Culver, Hoda, Arndt, Volker, Arun, Banu K., Arver, Brita, Bandera, Elisa V., Barile, Monica, Barkardottir, Rosa B., Barrowdale, Daniel, Beckmann, Matthias W., Benitez, Javier, Berchuck, Andrew, Bisogna, Maria, Bjorge, Line, Blomqvist, Carl, Blot, William, Bogdanova, Natalia, Bojesen, Anders, Bojesen, Stig E., Bolla, Manjeet K., Bonanni, Bernardo, Børresen-Dale, Anne Lise, Brauch, Hiltrud, Brennan, Paul, Brenner, Hermann, Bruinsma, Fiona, Brunet, Joan, Buhari, Shaik Ahmad, Burwinkel, Barbara, Butzow, Ralf, Buys, Saundra S., Cai, Qiuyin, Caldes, Trinidad, Campbell, Ian, Canniotto, Rikki, Chang-Claude, Jenny, Chiquette, Jocelyne, Choi, Ji Yeob, Claes, Kathleen B M, Cook, Linda S., Cox, Angela, Cramer, Daniel W., Cross, Simon S., Cybulski, Cezary, Czene, Kamila, Daly, Mary B., Damiola, Francesca, Dansonka-Mieszkowska, Agnieszka, Darabi, Hatef, Dennis, Joe, Devilee, Peter, Diez, Orland, Doherty, Jennifer A., Domchek, Susan M., Dorfling, Cecilia M., Dörk, Thilo, Dumont, Martine, Ehrencrona, Hans, Ejlertsen, Bent, Ellis, Steve, Engel, Christoph, Lee, Eunjung, Evans, D. Gareth, Fasching, Peter A., Feliubadalo, Lidia, Figueroa, Jonine, Flesch-Janys, Dieter, Fletcher, Olivia, Flyger, Henrik, Foretova, Lenka, Fostira, Florentia, Foulkes, William D., Fridley, Brooke L., Friedman, Eitan, Frost, Debra, Gambino, Gaetana, Ganz, Patricia A., Garber, Judy, García-Closas, Montserrat, Gentry-Maharaj, Aleksandra, Ghoussaini, Maya, Giles, Graham G., Glasspool, Rosalind, Godwin, Andrew K., Goldberg, Mark S., Goldgar, David E., González-Neira, Anna, Goode, Ellen L., Goodman, Marc T., Greene, Mark H., Gronwald, Jacek, Guénel, Pascal, Haiman, Christopher A., Hall, Per, Hallberg, Emily, Hamann, Ute, Hansen, Thomas V O, Harrington, Patricia A., Hartman, Mikael, Hassan, Norhashimah, Healey, Sue, Heitz, Florian, Herzog, Josef, Høgdall, Estrid, Høgdall, Claus K., Hogervorst, Frans B L, Hollestelle, Antoinette, Hopper, John L., Hulick, Peter J., Huzarski, Tomasz, Imyanitov, Evgeny N., Isaacs, Claudine, Ito, Hidemi, Jakubowska, Anna, Janavicius, Ramunas, Jensen, Allan, John, Esther M., Johnson, Nichola, Kabisch, Maria, Kang, Daehee, Kapuscinski, Miroslav, Karlan, Beth Y., Khan, Sofia, Kiemeney, Lambertus A., Kjaer, Susanne Kruger, Knight, Julia A., Konstantopoulou, Irene, Kosma, Veli Matti, Kristensen, Vessela, Kupryjanczyk, Jolanta, Kwong, Ava, De La Hoya, Miguel, Laitman, Yael, Lambrechts, Diether, Le, Nhu, De Leeneer, Kim, Lester, Jenny, Levine, Douglas A., Li, Jingmei, Lindblom, Annika, Long, Jirong, Lophatananon, Artitaya, Loud, Jennifer T., Lu, Karen, Lubinski, Jan, Mannermaa, Arto, Manoukian, Siranoush, Le Marchand, Loic, Margolin, Sara, Marme, Frederik, Massuger, Leon F A G, Matsuo, Keitaro, Mazoyer, Sylvie, McGuffog, Lesley, McLean, Catriona, McNeish, Iain, Meindl, Alfons, Menon, Usha, Mensenkamp, Arjen R., Milne, Roger L., Montagna, Marco, Moysich, Kirsten B., Muir, Kenneth, Mulligan, Anna Marie, Nathanson, Katherine L., Ness, Roberta B., Neuhausen, Susan L., Nevanlinna, Heli, Nord, Silje, Nussbaum, Robert L., Odunsi, Kunle, Offit, Kenneth, Olah, Edith, Olopade, Olufunmilayo I., Olson, Janet E., Olswold, Curtis, O'Malley, David, Orlow, Irene, Orr, Nick, Osorio, Ana, Park, Sue Kyung, Pearce, Celeste L., Pejovic, Tanja, Peterlongo, Paolo, Pfeiler, Georg, Phelan, Catherine M., Poole, Elizabeth M., Pylkäs, Katri, Radice, Paolo, Rantala, Johanna, Rashid, Muhammad Usman, Rennert, Gad, Rhenius, Valerie, Rhiem, Kerstin, Risch, Harvey A., Rodriguez, Gus, Rossing, Mary Anne, Rudolph, Anja, Salvesen, Helga B., Sangrajrang, Suleeporn, Sawyer, Elinor J., Schildkraut, Joellen M., Schmidt, Marjanka K., Schmutzler, Rita K., Sellers, Thomas A., Seynaeve, Caroline, Shah, Mitul, Shen, Chen Yang, Shu, Xiao Ou, Sieh, Weiva, Singer, Christian F., Sinilnikova, Olga M., Slager, Susan, Song, Honglin, Soucy, Penny, Southey, Melissa C., Stenmark-Askmalm, Marie, Stoppa-Lyonnet, Dominique, Sutter, Christian, Swerdlow, Anthony, Tchatchou, Sandrine, Teixeira, Manuel R., Teo, Soo H., Terry, Kathryn L., Terry, Mary Beth, Thomassen, Mads, Tibiletti, Maria Grazia, Tihomirova, Laima, Tognazzo, Silvia, Toland, Amanda Ewart, Tomlinson, Ian, Torres, Diana, Truong, Thérèse, Tseng, Chiu Chen, Tung, Nadine, Tworoger, Shelley S., Vachon, Celine, Van Den Ouweland, Ans M W, Van Doorn, Helena C., Van Rensburg, Elizabeth J., Van't Veer, Laura J., Vanderstichele, Adriaan, Vergote, Ignace, Vijai, Joseph, Wang, Qin, Wang-Gohrke, Shan, Weitzel, Jeffrey N., Wentzensen, Nicolas, Whittemore, Alice S., Wildiers, Hans, Winqvist, Robert, Wu, Anna H., Yannoukakos, Drakoulis, Yoon, Sook Yee, Yu, Jyh Cherng, Zheng, Wei, Zheng, Ying, Khanna, Kum Kum, Simard, Jacques, Monteiro, Alvaro N., French, Juliet D., Couch, Fergus J., Freedman, Matthew L., Easton, Douglas F., Dunning, Alison M., Pharoah, Paul D., Edwards, Stacey L., Chenevix-Trench, Georgia, Antoniou, Antonis C., Gayther, Simon A., Bowtell, David, DeFazio, Anna, Webb, Penny, Collonge-Rame, Marie Agnès, Damette, Alexandre, Barouk-Simonet, Emmanuelle, Bonnet, Françoise, Bubien, Virginie, Sevenet, Nicolas, Longy, Michel, Berthet, Pascaline, Vaur, Dominique, Castera, Laurent, Ferrer, Sandra Fert, Bignon, Yves Jean, Uhrhammer, Nancy, Coron, Fanny, Faivre, Laurence, Baurand, Amandine, Jacquot, Caroline, Bertolone, Geoffrey, Lizard, Sarab, Leroux, Dominique, Dreyfus, Hélène, Rebischung, Christine, Peysselon, Magalie, Peyrat, Jean Philippe, Fournier, Joëlle, Révillion, Françoise, Adenis, Claude, Vénat-Bouvet, Laurence, Léone, Mélanie, Boutry-Kryza, Nadia, Calender, Alain, Giraud, Sophie, Verny-Pierre, Carole, Lasset, Christine, Bonadona, Valérie, Barjhoux, Laure, Sobol, Hagay, Bourdon, Violaine, Noguchi, Tetsuro, Remenieras, Audrey, Coupier, Isabelle, Pujol, Pascal, Sokolowska, Johanna, Bronner, Myriam, Delnatte, Capucine, Bézieau, Stéphane, Mari, Véronique, Gauthier-Villars, Marion, Buecher, Bruno, Rouleau, Etienne, Golmard, Lisa, Moncoutier, Virginie, Belotti, Muriel, De Pauw, Antoine, Elan, Camille, Fourme, Emmanuelle, Birot, Anne Marie, Saule, Claire, Laurent, Maïté, Houdayer, Claude, Lesueur, Fabienne, Mebirouk, Noura, Coulet, Florence, Colas, Chrystelle, Soubrier, Florent, Warcoin, Mathilde, Prieur, Fabienne, Lebrun, Marine, Kientz, Caroline, Muller, Danièle, Fricker, Jean Pierre, Toulas, Christine, Guimbaud, Rosine, Gladieff, Laurence, Feillel, Viviane, Mortemousque, Isabelle, Bressac-De-Paillerets, Brigitte, Caron, Olivier, Guillaud-Bataille, Marine, Gregory, Helen, Miedzybrodzka, Zosia, Morrison, Patrick J., Donaldson, Alan, Rogers, Mark T., Kennedy, M. John, Porteous, Mary E., Brady, Angela, Barwell, Julian, Foo, Claire, Lalloo, Fiona, Side, Lucy E., Eason, Jacqueline, Henderson, Alex, Walker, Lisa, Cook, Jackie, Snape, Katie, Murray, Alex, McCann, Emma, Rookus, M. A., Van Leeuwen, F. E., Van Der Kolk, L. E., Schmidt, M. K., Russell, N. S., De Lange, J. L., Wijnands, R., Collée, J. M., Hooning, M. J., Seynaeve, C., Van Deurzen, C. H M, Obdeijn, I. M., Van Asperen, C. J., Tollenaar, R. A E M, Van Cronenburg, T. C T E F, Kets, C. M., Ausems, M. G E M, Van Der Pol, C. C., Van Os, T. A M, Waisfisz, Q., Meijers-Heijboer, H. E J, Gómez-Garcia, E. B., Oosterwijk, J. C., Mourits, M. J., De Bock, G. H., Vasen, H. F., Siesling, S., Verloop, J., Overbeek, L. I H, Fox, Stephen, Kirk, Judy, Lindeman, Geoff, Price, Melanie, NIH - National Cancer Institute (NCI) (Estados Unidos), National Health and Medical Research Council (Australia), Victorian Health Promotion Foundation, Dutch Cancer Society (Holanda), Breast Cancer Research Trust, Instituto de Salud Carlos III, Lon V. Smith Foundation, Federal Ministry of Education & Research (Alemania), Finlands Akademi (Finlandia), United States Army Medical Research and Development Command, California Breast Cancer Research Program, German Cancer Aid, Canadian Institutes of Health Research, Ministère de Économie, Innovation et Exportation (Canadá), Ministry of Higher Education (Malasia), National Medical Research Council (Singapur), University of Oulu (Finlandia), Yorkshire Cancer Research, Hellenic Cooperative Oncology Group, California Cancer Research Program, Danish Cancer Society, Ministry of Science and Higher Education (Polonia), Asociación Española Contra el Cáncer, University of Kansas. Cancer Center (Estados Unidos), Hungarian Research Grants, Norwegian EEA Financial Mechanism, Canadian Breast Cancer Network, NIH - National Cancer Institute (NCI). Specialized Programs of Research Excellence (SPOREs) (Estados Unidos), Congressionally Directed Medical Research Programs (Estados Unidos), NRG Oncology National (Estados Unidos), Unión Europea. Comisión Europea. 7 Programa Marco, Medical Oncology, Obstetrics & Gynecology, Clinical Genetics, 1 Department of Preventive Medicine, Keck School of MediCenter, Kansas City, Kansas 66160, USA. 90 Susanne Levy Gertner Oncogenetics Unit, Sheba Medical Center, Tel-Hashomer 52621, Israel. 91 Section of Genetic Oncology, Department of Laboratory Medicine, University and University Hospital of Pisa, Pisa 56126, Italy. 92 UCLA Schools of Medicine and Public Health, Division of Cancer Prevention & Control Research, Jonsson Comprehensive Cancer Center, Los Angeles, California 90024, USA. 93 Cancer Risk and Prevention Clinic, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 94 Division of Genetics and Epidemiology, The Institute of Cancer Research, London SW7 3RP, UK. 95Women’s Cancer, UCL EGA Institute for Women’s Health, London WC1E 6AU, UK. 96 Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Melbourne, Victoria 3010, Australia. 97 Cancer Research UK Clinical Trials Unit, The BeatsonWest of Scotland Cancer Centre, Glasgow G12 0YN, UK. 98 Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, Kansas 66160, USA. 99 Division of Clinical Epidemiology, Royal Victoria Hospital, McGill University, Montreal, Que´bec H3A 1A1, Canada. 100 Department of Medicine, McGill University, Montreal, Que´bec H3A 1A1, Canada. 101 Department of Dermatology, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84132, USA. 102 Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota 55902, USA. 103 Cancer Prevention and Control, Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 104Community and Population Health Research Institute, Department of Biomedical Sciences, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 105 Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Rockville, Maryland 20892, USA. 106 Department of Genetics and Pathology, Pomeranian Medical University, 70-204 Szczecin, Poland. 107 Environmental Epidemiology of Cancer, Center for Research in Epidemiology and Population Health, INSERM, 94805 Villejuif, France. 108 University Paris- Sud, 91405 Villejuif, France. 109 Molecular Genetics of Breast Cancer, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 110 Center for Genomic Medicine, Rigshospitalet, Copenhagen University Hospital, 2100 Copenhagen, Denmark. 111 Department of Oncology, Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge CB1 8RN, UK. 112 Saw Swee Hock School of Public Health, National University of Singapore Singapore 119077, Singapore. 113 Breast Cancer Research Unit, Cancer Research Institute, University Malaya Medical Centre, 50603 Kuala Lumpur, Malaysia. 114 Cancer Research Initiatives Foundation, Subang Jaya, 47500 Selangor, Malaysia. 115 Department of Gynecology and Gynecologic Oncology, Kliniken Essen-Mitte, 45136 Essen, Germany. 116 Department of Gynecology and Gynecologic Oncology, Dr Horst Schmidt Kliniken Wiesbaden, 65199 Wiesbaden, Germany. 117 Clinical Cancer Genetics, for the City of Hope Clinical Cancer Genetics Community Research Network, Duarte California 91010, USA. 118 Molecular Unit, Department of Pathology, Herlev Hospital, University of Copenhagen, 2730 Copenhagen, Denmark. 119 Department of Virus, Lifestyle and Genes, Danish Cancer Society Research Center, DK-2100 Copenhagen, Denmark. 120 Department of Gynecology, Rigshospitalet, University of Copenhagen, 2100 Copenhagen, Denmark. 121 Family Cancer Clinic, Netherlands Cancer Institute, 1006 Amsterdam, The Netherlands. 122 Department of Medical Oncology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 Rotterdam, The Netherlands. 123 Center for Medical Genetics, NorthShore University Health System, Evanston, Illinois 60201, USA. 124 N.N. Petrov Institute of Oncology, St Petersburg 197758, Russia. 125 Lombardi Comprehensive Cancer Center, Georgetown University, Washington District of Columbia 20057, USA. 126 Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Aichi 464-8681, Japan. 127 State Research Institute Centre for Innovative Medicine, LT-01102 Vilnius, Lithuania. 128 Department of Epidemiology, Cancer Prevention Institute of California, Fremont, California 94538, USA. 129 Department of Preventive Medicine, Seoul National University College of Medicine, Seoul 08826, Korea. 130 Centre for Epidemiology and Biostatistics, University of Melbourne, Melbourne, Victoria 3010, Australia. 131Women’s Cancer Program at the Samuel Oschin Comprehensive Cancer Institute, Cedars-Sinai Medical Center, Los Angeles, California 90048, USA. 132 Radboud University Medical Centre, Radboud Institute for Health Sciences, 6500 Nijmegen, The Netherlands. 133 Prosserman Centre for Health Research, Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario M5G 1X5, Canada. 134 Division of Epidemiology, Dalla Lana School of Public Health, University of Toronto, Toronto, Ontario M5T 3M7, Canada. 135 Imaging Center, Department of Clinical Pathology, Kuopio University Hospital, 70210 Kuopio, Finland. 136 Cancer Center, Kuopio University Hospital, 70210 Kuopio, Finland. 137 Institute of Clinical Medicine, Pathology and Forensic Medicine, University of Eastern Finland, 70210 Kuopio, Finland. 138 Department of Clinical Molecular Biology, Oslo University Hospital, University of Oslo, 1478 Oslo, Norway. 139 The Hong Kong Hereditary Breast Cancer Family Registry, Cancer Genetics Center, Hong Kong Sanatorium and Hospital, Hong Kong, China. 140 Department of Surgery, The University of Hong Kong, Hong Kong, China. 141Vesalius Research Center, VIB, 3000 Leuven, Belgium. 142 Laboratory for Translational Genetics, Department of Oncology, University of Leuven, 3000 Leuven, Belgium. 143 Department of Molecular Medicine and Surgery, Karolinska Institutet, SE-171 77 Stockholm, Sweden. 144 Division of Health Sciences, Warwick Medical School, Warwick University, Coventry CV4 7AL, UK. 145 Department of Gynecologic Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 146 Unit of Medical Genetics, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale Tumori (INT), 20133 Milan, Italy. 147 University of Hawaii Cancer Center, Honolulu, Hawaii 96813, USA. 148 Department of Oncology - Pathology, Karolinska Institutet, SE- 171 77 Stockholm, Sweden. 149 National Center for Tumour Diseases, University of Heidelberg, 69117 Heidelberg, Germany. 150 Department of Gynaecology, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 151 Department of Preventive Medicine, Kyushu University Faculty of Medical Sciences, Fukuoka 812-8582, Japan. 152 Anatomical Pathology, The Alfred Hospital, Melbourne, Victoria 3004, Australia. 153 Institute of Cancer Sciences, University of Glasgow, Wolfson Wohl Cancer Research Centre, Beatson Institute for Cancer Research, Glasgow G61 1BD, UK. 154 Division of Gynaecology and Obstetrics, Technische Universita¨t Mu¨nchen, 81675 Munich, Germany. 155 Department of Human Genetics, Radboud University Medical Centre, 6500 Nijmegen, The Netherlands. 156 Immunology and Molecular Oncology Unit, Instituto Oncologico Veneto IOV, IRCCS, 35128 Padua, Italy. 157 Department of Cancer Prevention and Control, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 158 Institute of Population Health, University of Manchester, Manchester M13 9PL, UK. 159 Laboratory Medicine Program, University Health Network, Toronto, Ontario M5G 1L7, Canada. 160 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Ontario M5G 1L7, Canada. 161 The University of Texas School of Public Health, Houston, Texas 77030, USA. 162 Department of Population Sciences, Beckman Research Institute of City of Hope, Duarte, California 91010, USA. 163 Department of Medicine and Genetics, University of California, San Francisco, California 94143, USA. 164 Department of Gynecological Oncology, Roswell Park Cancer Institute, Buffalo, New York 14263, USA. 165 Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 166 Department of Molecular Genetics, National Institute of Oncology, 1122 Budapest, Hungary. 167 Center for Clinical Cancer Genetics and Global Health, University of Chicago Medical Center, Chicago, Illinois 60637, USA. 168 The Ohio State University and the James Cancer Center, Columbus, Ohio 43210, USA. 169 Department of Epidemiology and Biostatistics, Memorial Sloan Kettering Cancer Center, New York 10017, USA. 170 Human Genetics Group, Human Cancer Genetics Program, Spanish National Cancer Centre (CNIO), 28019 Madrid, Spain. 171 Biomedical Network on Rare Diseases (CIBERER), 28029 Madrid, Spain. 172 Department of Surgery, Seoul National University College of Medicine, Seoul, 03080 Korea. 173 Department of Obstetrics and Gynecology, Oregon Health and Science University, Portland, Oregon 97239, USA. 174 Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97239, USA. 175 IFOM, The FIRC (Italian Foundation for Cancer Research) Institute of Molecular Oncology, 16 20139 Milan, Italy. 176 Department of Obstetrics and Gynecology, Comprehensive Cancer Center, Medical University of Vienna, 1090 Vienna, Austria. 177 Department of Cancer Epidemiology, Moffitt Cancer Center, Tampa, Florida 33606, USA. 178 Channing Division of Network Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 179 Department of Epidemiology, Harvard TH Chan School of Public Health, Boston, Massachusetts 02115, USA. 180 Laboratory of Cancer Genetics and Tumour Biology, Northern Finland Laboratory Centre NordLab, FI-90014 Oulu, Finland. 181 Laboratory of Cancer Genetics and Tumour Biology, Department of Clinical Chemistry and Biocenter Oulu, University of Oulu, FI-90014 Oulu, Finland. 182 Unit of Molecular Bases of Genetic Risk and Genetic Testing, Department of Preventive and Predictive Medicine, Fondazione IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico) Istituto Nazionale dei Tumori (INT),cine, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, California 90033, USA. 2 Department of Oncology, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 3 QIMR Berghofer Medical Research Institute, Brisbane, Queensland 4029, Australia. 4 Department of Public Health and Primary Care, Centre for Cancer Genetic Epidemiology, University of Cambridge, Cambridge CB1 8RN, UK. 5 Medical College, Xiamen University, Xiamen 361102, China. 6 Department of Medical Oncology, The Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, Massachusetts 02215, USA. 7 Department of Clinical Genetics, Helsinki University Hospital, University of Helsinki, Helsinki 00029 HUS, Finland. 8 Lunenfeld-Tanenbaum Research Institute of Mount Sinai Hospital, Toronto, Ontario Canada, M5G 1X5. 9 Department of Molecular Genetics, University of Toronto, Toronto, OntarioCanada, M5S 1A8. 10 Department of Epidemiology, Genetic Epidemiology Research Institute, School of Medicine, University of California Irvine, Irvine, California 92697, USA. 11 Division of Clinical Epidemiology and Aging Research, German Cancer Research Center (DKFZ), Heidelberg, 69120, Germany. 12 University of Texas MD Anderson Cancer Center, Houston, Texas 77030, USA. 13 Department of Oncology, Karolinska University Hospital, Stockholm 171 77, Sweden. 14 Cancer Prevention and Control, Rutgers Cancer Institute of New Jersey, New Brunswick, New Jersey 08903, USA. 15 Division of Cancer Prevention and Genetics, Istituto Europeo di Oncologia, Milan 20141, Italy. 16 Department of Pathology, Landspitali University Hospital and BMC (Biomedical Centre), Faculty of Medicine, University of Iceland, Reykjavik 600169- 2039, Iceland. 17 University Hospital Erlangen, Department of Gynecology and Obstetrics, Friedrich-Alexander-University Erlangen-Nuremberg, Comprehensive Cancer Center Erlangen-EMN, Erlangen 91054, Germany. 18 Human Cancer Genetics Program, Spanish National Cancer Research Centre, Madrid E-28029, Spain. 19 Centro de Investigacio´n en Red de Enfermedades Raras, Valencia 28029, Spain. 20 Department of Obstetrics and Gynecology, Duke University Medical Center, Durham, North Carolina 27710, USA. 21 Gynecology Service, Department of Surgery, Memorial Sloan-Kettering Cancer Center, New York 10065, USA. 22 Department of Gynecology and Obstetrics, Haukeland University Hospital, 5021 Bergen, Norway. 23 Centre for Cancer Biomarkers, Department of Clinical Science, University of Bergen, N-5020 Bergen, Norway. 24 Department of Oncology, Helsinki University Hospital, University of Helsinki, Helsinki FIN-00029, Finland. 25 Division of Epidemiology, Department of Medicine, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, Tennessee 37203, USA. 26 International Epidemiology Institute, Rockville, Maryland 20850, USA. 27 Gynaecology Research Unit, Hannover Medical School, Hannover D-30625, Germany. 28 Department of Clinical Genetics, Vejle Hospital, Vejle 7100, Denmark. 29 Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen 2200, Denmark. 30 Department of Clinical Biochemistry, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 31 Copenhagen General Population Study, Herlev Hospital, Copenhagen University Hospital, Herlev 2730, Denmark. 32 Department of Genetics, Institute for Cancer Research, Oslo University Hospital Radiumhospitalet, Oslo N-0310, Norway. 33 K.G. Jebsen Center for Breast Cancer Research, Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo N-0310, Norway. 34 Dr Margarete Fischer- Bosch-Institute of Clinical Pharmacology, Stuttgart D-70376, Germany. 35 University of Tu¨bingen, Tu¨bingen 72074, Germany. 36 German Cancer Consortium (DKTK), German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 37 International Agency for Research on Cancer, Lyon 69008, France. 38 Division of Preventive Oncology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 39 Cancer Epidemiology Centre, Cancer Council Victoria, Melbourne, Victoria 3004, Australia. 40 Genetic Counseling Unit, Hereditary Cancer Program, IDIBGI (Institut d’Investigacio´ Biome`dica de Girona), Catalan Institute of Oncology, Girona 08908, Spain. 41 Department of Surgery, National University Health System, Singapore 119077, Singapore. 42 Molecular Epidemiology Group, German Cancer Research Center (DKFZ), Heidelberg 69120, Germany. 43 Department of Obstetrics and Gynecology, University of Heidelberg, Heidelberg 69120, Germany. 44 Department of Obstetrics and Gynecology, University of Helsinki and Helsinki University Central Hospital, Helsinki 00029 HUS, Finland. 45 Department of Pathology, Helsinki University Central Hospital, Helsinki 00029, Finland. 46 Department of Medicine, Huntsman Cancer Institute, University of Utah School of Medicine, Salt Lake City, Utah 84112, USA. 47 Molecular Oncology Laboratory, Hospital Clinico San Carlos, IdISSC (El Instituto de Investigacio´n Sanitaria del Hospital Clı ´nico San Carlos), Madrid 28040, Spain. 48 Cancer Genetics Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia. 49 Cancer Pathology & Prevention, Division of Cancer Prevention and Population Sciences, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo 14263, New York, USA. 50 Division of Cancer Epidemiology, German Cancer Research Center (DKFZ), Heidelberg 69121, Germany. 51 University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Hamburg 20246, Germany. 52 Unite´ de recherche en sante´ des populations, Centre des maladies du sein Descheˆnes-Fabia, Centre de recherche FRSQ du Centre hospitalier affilie´ universitaire de Que´bec, Que´bec City, Que´bec Canada, G1J 1Z4. 53 Cancer Research Institute, Seoul National University, Seoul 08826, Korea. 54 Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul 03080, Korea. 55 Center for Medical Genetics, Ghent University, Ghent 9000, Belgium. 56 Division of Epidemiology and Biostatistics, Department of Internal Medicine, University of New Mexico, Albuquerque, New Mexico 87131, USA. 57 Sheffield Cancer Research, Department of Oncology, University of Sheffield, Sheffield S10 2TN, UK. 58 Harvard HT Chan School of Public Health, Boston, Massachusetts 02115, USA. 59 Obstetrics and Gynecology Epidemiology Center, Brigham andWomen’s Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA. 60 Academic Unit of Pathology, Department of Neuroscience, University of Sheffield, Sheffield S10 2TN, UK. 61 Department of Genetics and Pathology, Pomeranian Medical University, Szczecin 70-115, Poland. 62 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm SE-171 77, Sweden. 63 Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111, USA. 64 INSERM U1052, CNRS UMR5286, Universite´ Lyon, Centre de Recherche en Cance´rologie de Lyon, Lyon 69373, France. 65 Department of Pathology and Laboratory Diagnostics the Maria Sklodowska Curie Memorial Cancer Center and Institute of Oncology,Warsaw 44-101, Poland. 66 Department of Pathology, Leiden University Medical Center, Leiden 2333, The Netherlands. 67 Department of Human Genetics, Leiden University Medical Center, Leiden 2333, The Netherlands. 68 Oncogenetics Group, University Hospital Vall d’Hebron, Vall d’Hebron Institute of Oncology (VHIO) and Universitat Auto`noma de Barcelona, Barcelona, 186 Centre of Familial Breast and Ovarian Cancer, Department of Gynaecology and Obstetrics and Centre for Integrated Oncology (CIO), Center for Molecular Medicine Cologne (CMMC), University Hospital of Cologne, 50931 Cologne, Germany. 187Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, Connecticut 06510, USA. 188Division of Gynecologic Oncology, NorthShore University HealthSystem, Evanston, Illinois 60201, USA. 189 Program in Epidemiology, Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington 98109, USA. 190Department of Epidemiology, University of Washington, Seattle, Washington 98109, USA. 191National Cancer Institute, Bangkok 10400, Thailand. 192 Research Oncology, Guy’s Hospital, King’s College London, London SE1 9RT, UK. 193Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina 27710, USA. 194 Cancer Control and Population Sciences, Duke Cancer Institute, Durham, North Carolina 27710, USA. 195Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, 1066 CX Amsterdam, The Netherlands. 196Division of Molecular Gyneco-Oncology, Department of Gynaecology and Obstetrics, University Hospital of Cologne, 50676 Cologne, Germany. 197 Center for Integrated Oncology, University Hospital of Cologne, 50676 Cologne, Germany. 198 Center for Molecular Medicine, University Hospital of Cologne, 50676 Cologne, Germany. 199 Center of Familial Breast and Ovarian Cancer, University Hospital of Cologne, 50676 Cologne, Germany. 200 Taiwan Biobank, Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan. 201 School of Public Health, China Medical University, Taichung 404, Taiwan. 202Department of Health Research and Policy - Epidemiology, Stanford University School of Medicine, Stanford California 94305, USA. 203 Unite´ Mixte de Ge´ne´tique Constitutionnelle des Cancers Fre´quents, Hospices Civils de Lyon – Centre Le´on Be´rard, Lyon 69008, France. 204 INSERM U1052, CNRS UMR5286, Universite´ Lyon 1, Centre de Recherche en Cance´rologie de Lyon, Lyon 69003, France. 205Department of Pathology, University of Melbourne, Parkville, Victoria 3010, Australia. 206Division of Clinical Genetics, Department of Clinical and Experimental Medicine, Linko¨ping University, 581 83 Linko¨ping, Sweden. 207 Institut Curie, Department of Tumour Biology, Paris, France, Institut Curie, INSERM U830, 75248 Paris, France. 208Universite´ Paris Descartes, Sorbonne Paris Cite´, 75270 Paris, France. 209 Institute of Human Genetics, Department of Human Genetics, University Hospital Heidelberg, 69120 Heidelberg, Germany. 210Department of Genetics, Portuguese Oncology Institute, Porto 4200-072, Portugal. 211 Biomedical Sciences Institute (ICBAS), Porto University, Porto 4099-002, Portugal. 212Department of Epidemiology, Mailman School of Public Health, Columbia University, New York 10027, USA. 213Department of Clinical Genetics, Odense University Hospital, 5000 Odense C, Denmark. 214UO Anatomia Patologica, Ospedale di Circolo-Universita` dell’Insubria, 21100 Varese, Italy. 215 Latvian Biomedical Research and Study Centre, Riga LV-1067, Latvia. 216 Immunology and Molecular Oncology Unit, Istituto Oncologico Veneto IOV - IRCCS (Istituto Di Ricovero e Cura a Carattere Scientifico), 64 - 35128 Padua, Italy. 217Department of Molecular Virology, Immunology and Medical Genetics, The Ohio State University, Columbus, Ohio 43210, USA. 218Wellcome Trust Centre for Human Genetics and Oxford Biomedical Research Centre, University of Oxford, Oxford OX3 7BN, UK. 219 Institute of Human Genetics, Pontificia Universidad Javeriana, Cra. 7 #40-62 Bogota, Colombia. 220Department of Medical Oncology, Beth Israel Deaconess Medical Center, Boston, Massachusetts 02215, USA. 221Department of Clinical Genetics, Erasmus University Medical Center, 3015 CE Rotterdam, The Netherlands. 222Department of Gynecology, Family Cancer Clinic, Erasmus MC Cancer Institute, 3015 CE Rotterdam, The Netherlands. 223Division of Gynecological Oncology, Department of Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 224University Hospital Ulm, 89069 Ulm, Germany. 225Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda Maryland 20892, USA. 226 Multidisciplinary Breast Center, Department of General Medical Oncology, University Hospitals Leuven, B-3000 Leuven, Belgium. 227 Molecular Diagnostics Laboratory, IRRP, National Centre for Scientific Research ‘Demokritos’, Athens 153 10, Greece. 228 Cancer Research Initiatives Foundation, Sime Darby Medical Centre, 47500 Subang Jaya, Malaysia. 229 University Malaya Cancer Research Institute, Faculty of Medicine, University Malaya Medical Centre, University Malaya, 59100 Kuala Lumpur, Malaysia. 230Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, 114 Taiwan. 231 Shanghai Center for Disease Control and Prevention, Shanghai, China. 232 Cancer Epidemiology Program, Division of Population Sciences, H. Lee Moffitt Cancer Center & Research Institute, Tampa, Florida 33612, USA. 233Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. 234 Peter MacCallum Cancer Centre, East Melbourne, Victoria 3002, Australia. 235 Sir Peter MacCallum Cancer Centre Department of Oncology, University of Melbourne, Parkville, Victoria 3052, Australia. 236 Ovarian Cancer Action Research Centre, Department of Surgery and Cancer, Imperial College London, London W12 0HS, UK. 237 Department of Biochemistry and Molecular Biology, University of Melbourne, Parkville, Victoria 3052, Australia. 238 Department of Gynaecological Oncology, Westmead Institute for Cancer Research, Westmead Hospital Westmead, New South Wales 2145, Australia., Tyrer, Jonathan [0000-0003-3724-4757], Dennis, Joe [0000-0003-4591-1214], Rhenius, Valerie [0000-0003-4215-3235], Song, Honglin [0000-0001-5076-7371], Wang, Jean [0000-0002-9139-0627], Easton, Douglas [0000-0003-2444-3247], Dunning, Alison [0000-0001-6651-7166], Pharoah, Paul [0000-0001-8494-732X], Antoniou, Antonis [0000-0001-9223-3116], Apollo - University of Cambridge Repository, Epidemiology and Data Science, EMGO - Quality of care, Anesthesiology, Human genetics, CCA - Cancer biology, and VU University medical center
Subjects: endocrine system diseases, Messenger, IDENTIFIES 3, MODIFIERS, Brjóstakrabbamein, BRCA2 MUTATION CARRIERS, Medicine and Health Sciences, GWAS, INVESTIGATORS, African Continental Ancestry Group, Asian Continental Ancestry Group, Breast Neoplasms, Chromosomes, Human, Pair 19, Female, Genome-Wide Association Study, Genotype, Humans, Ovarian Neoplasms, RNA, Messenger, Alleles, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, skin and connective tissue diseases, COMMON VARIANTS, EPITHELIAL-CELLS, Single Nucleotide, female genital diseases and pregnancy complications, NAF12, Medical Genetics, Human, endocrine system, Science, Chromosomes, Human, Pair 19/genetics, Black People, Breast Neoplasms/genetics, Chromosomes, Article, Ovarian Neoplasms/genetics, SDG 3 - Good Health and Well-being, Asian People, REVEALS, Polymorphism, GENOME-WIDE ASSOCIATION, Krabbamein, Medicinsk genetik, Cancer och onkologi, Pair 19, Arfgengi, GENE, Eggjastokkar, Cancer and Oncology, RNA, BRCA1 Protein/genetics
Abstract: A locus at 19p13 is associated with breast cancer (BC) and ovarian cancer (OC) risk. Here we analyse 438 SNPs in this region in 46,451 BC and 15,438 OC cases, 15,252 BRCA1 mutation carriers and 73,444 controls and identify 13 candidate causal SNPs associated with serous OC (P=9.2 × 10−20), ER-negative BC (P=1.1 × 10−13), BRCA1-associated BC (P=7.7 × 10−16) and triple negative BC (P-diff=2 × 10−5). Genotype-gene expression associations are identified for candidate target genes ANKLE1 (P=2 × 10−3) and ABHD8 (P, A region on chromosome 19p13 is associated with the risk of developing ovarian and breast cancer. Here, the authors genotyped SNPs in this region in thousands of breast and ovarian cancer patients and identified SNPs associated with three genes, which were analysed with functional studies.
Published: 2016
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30. The genetics of blood pressure regulation and its target organs from association studies in 342,415 individuals

Author: Timo A. Lakka, Kathleen Stirrups, Jean Ferrières, Ying Wu, Gulum Kosova, Toby Johnson, Heather M. Stringham, Bruce M. Psaty, Bruna Gigante, Göran Hallmans, Cornelia M. van Duijn, Kae Woei Liang, Niclas Eriksson, N. William Rayner, Lynda M. Rose, Stavroula Kanoni, Xueling Sim, Evangelos Evangelou, Philippe Froguel, Michel Burnier, Andrew P. Morris, Olle Melander, Martin Farrall, Albert V. Smith, Brendan J. Keating, Thomas Illig, Johan Sundström, Dorret I. Boomsma, Kate Witkowska, Ellen M. Schmidt, Aki S. Havulinna, Ann-Kristin Petersen, Paul F. O'Reilly, Young Jin Kim, Kari Kuulasmaa, Tom Wilsgaard, John D. Eicher, Marcus E. Kleber, Francis S. Collins, Rona J. Strawbridge, Ronald M. Krauss, Fotios Drenos, Stuart K. Kim, Ken K. Ong, Pascal Bovet, Danish Saleheen, Jaspal S. Kooner, Karl-Heinz Herzig, Tien Yin Wong, Benjamin F. Voight, Stefania Bandinelli, Stéphane Lobbens, Colin A. McKenzie, Jing Hua Zhao, Terrence Forrester, Louise A. Donnelly, Alice Stanton, Jean Dallongeville, Kirill V. Tarasov, Narisu Narisu, Jürgen Gräßler, Luigi Ferrucci, Peter S. Sever, Paul Elliott, Tune H. Pers, Andrew J. Smith, Tomas Axelsson, Young Ah Shin, Nora Franceschini, James F. Wilson, Vilmundur Gudnason, Kati Kristiansson, Andrew A. Hicks, Kent D. Taylor, Genovefa Kolovou, Andrew D. Morris, André G. Uitterlinden, Serena Sanna, Xiuqing Guo, Honghuang Lin, Aravinda Chakravarti, Wayne Huey-Herng Sheu, Panos Deloukas, Linda S. Adair, Diana Kuh, Murielle Bochud, Eric Boerwinkle, Inger Njølstad, Meena Kumari, Norman Klopp, Leo-Pekka Lyytikäinen, Steven C. Hunt, Weihua Zhang, Tõnu Esko, Pierre Meneton, Markus Perola, Erik P A Van Iperen, Georg Ehret, Veikko Salomaa, Lars Lind, Zoltán Kutalik, Cristiano Fava, Caroline Hayward, Hugh S. Markus, Teresa Ferreira, Stefan R. Bornstein, Vasyl Pihur, Patricia B. Munroe, Anne U. Jackson, Eirini Marouli, Gabriele Müller, Damiano Baldassarre, Jacques E. Rossouw, Dan E. Arking, Maija Hassinen, Nicholas J. Wareham, Robert Roberts, Daniel I. Chasman, I. Shou Chang, Sylvain Sebert, Tove Fall, Roby Joehanes, Patrik K. E. Magnusson, John C. Chambers, Peter Vollenweider, Wen Jane Lee, Dmitry Shungin, Mathias Gorski, Christopher Newton-Cheh, Anders Franco-Cereceda, Ching-Yu Cheng, Yun Kyoung Kim, Ruth J. F. Loos, Lude Franke, Karen L. Mohlke, Yii-Der Ida Chen, Carlos Iribarren, Martina Müller-Nurasyid, Alexander Teumer, Andrew D. Johnson, Antonella Mulas, Ulf Gyllensten, Martin D. Tobin, George Dedoussis, Rainford J. Wilks, Joshua C. Bis, Beverley Balkau, Jie Yao, Frida Renström, Themistocles L. Assimes, Morris Brown, Inês Barroso, Hyun Min Kang, Loic Yengo, Mika Kähönen, Christopher J. Groves, Kirsti Kvaløy, Rainer Rauramaa, Heribert Schunkert, Satu Männistö, Marjo-Riitta Järvelin, Nancy L. Pedersen, Karl Gertow, Rick Jansen, Thomas Quertermous, Jarmo Virtamo, Lazaros Lataniotis, Serge Hercberg, Paul M. Ridker, Osorio Meirelles, Jostein Holmen, Phil Howard, G. Kees Hovingh, Jeanette Erdmann, Jong-Young Lee, Peter Schwarz, Ramaiah Nagaraja, Elizabeth Theusch, Wei Zhao, Sonia Shah, Chao A. Hsiung, Santhi K. Ganesh, Richard S. Cooper, John M. C. Connell, Jian'an Luan, Graciela E. Delgado, Eric Kim, Daniel Levy, Li Lin, Jerome I. Rotter, Andres Metspalu, Nabila Bouatia-Naji, Christopher J. O'Donnell, Roberto Elosua, Andrew Wong, Alanna C. Morrison, Juha Saltevo, Michael R. Barnes, Alan B. Weder, Kay-Tee Khaw, Leena Moilanen, Peter S. Chines, Claudia Langenberg, Marika Kaakinen, Asif Rasheed, Annette Peters, Angela Döring, Alena Stančáková, Richard A. Jensen, Jaana Lindström, Alison H. Goodall, Toshiko Tanaka, Loukianos S. Rallidis, Dabeeru C. Rao, Ann-Christine Syvänen, Alun Evans, Brenda W.J.H. Penninx, Sarah Edkins, Xiaohui Li, Neil Poulter, Jouko Saramies, Ulf de Faire, Walter Palmas, Jaakko Tuomilehto, Louise V. Wain, Cristina Menni, Stephen Bevan, Maria X. Sosa, Nanette R. Lee, Anuj Goel, Germaine C. Verwoert, Kjell Nikus, Helen R. Warren, May E. Montasser, Ren-Hua Chung, Francesco Gianfagna, Kristian Hveem, Rainer Rettig, Unnur Thorsteinsdottir, Lori L. Bonnycastle, Tim D. Spector, Paul W. Franks, Bamidele O. Tayo, Ilja M. Nolte, John Danesh, E. Shyong Tai, Mika Kivimäki, Devin Absher, Oddgeir L. Holmen, Per Eriksson, Pirjo Komulainen, Peter P. Pramstaller, Cameron D. Palmer, He Gao, Elena Tremoli, H.-Erich Wichmann, Myriam Fornage, Gyda Bjornsdottir, Afshin Parsa, Anders Hamsten, Terho Lehtimäki, Lasse Folkersen, Janine F. Felix, Anna F. Dominiczak, Hinco J. Gierman, Edward G. Lakatta, Alex S. F. Doney, Erik Ingelsson, Colin N. A. Palmer, Najaf Amin, Hugh Watkins, Johanna Kuusisto, Vladan Mijatovic, Mark I. McCarthy, Joel N. Hirschhorn, Winfried März, Nilesh J. Samani, Stefan Enroth, Mark J. Caulfield, Gudmar Thorleifsson, Tsun-Po Yang, François Mach, Cristen J. Willer, Claudia P. Cabrera, Aline Wagner, Michael Boehnke, Elias Salfati, Sekar Kathiresan, Ramachandran S. Vasan, Franco Giulianini, Harm-Jan Westra, Harold Snieder, Mark O. Goodarzi, M. Arfan Ikram, Fred Paccaud, Johannes H. Smit, Anna-Liisa Hartikainen, Xiaofeng Zhu, Markku Laakso, Ahmad Vaez, Albert Hofman, Amy J. Swift, Maria Hughes, I. Te Lee, Aroon D. Hingorani, Matti Uusitupa, Oscar H. Franco, Kenneth Rice, Veronique Vitart, Ross M. Fraser, Jouke-Jan Hottenga, Kari Stefansson, Dhananjay Vaidya, Johns Hopkins University, School of Medicine, Hôpitaux Universitaires de Genève (HUG), Saw Swee Hock School of Public Health, National University of Singapore (NUS), The Wellcome Trust Centre for Human Genetics [Oxford], University of Oxford [Oxford], Brigham and Women's Hospital [Boston], Harvard Medical School [Boston] (HMS), Department of Biostatistics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Michigan System, Department of Computational Medicine and Bioinformatics (DCM&B), Queen Mary University of London (QMUL), GlaxoSmithKline, Glaxo Smith Kline, deCODE genetics [Reykjavik], University of Cambridge [UK] (CAM), University of Dundee, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Karolinska University Hospital [Stockholm], Umea University Hospital, Lund University [Lund], Queen's University [Belfast] (QUB), National Institutes of Health, Department of Genomics of Common Disease, Imperial College London, Institut National de la Santé et de la Recherche Médicale (INSERM), Université Paris Descartes - Paris 5 (UPD5), National Institute of Health and Welfare, Institute for Molecular Medicine Finland (FIMM), University College London Hospitals (UCLH), University Hospital of Heidelberg, Harbor UCLA Medical Center [Torrance, Ca.], University of Tampere, University of Verona (UNIVR), Uppsala University Hospital, Department of Genetics, University Medical Center Groningen, University of Groningen, Groningen, Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], Stanford University School of Medicine [CA, USA], Medical School University of Athens, Partenaires INRAE, Children's Hospital Oakland Research Institute, Boston Children's Hospital, Broad Institute of Harvard and MIT, University of Copenhagen = Københavns Universitet (KU), Statens Serum Institut [Copenhagen], Framingham Heart Dis Epidemiol Study, Department of Psychiatry, VU University Medical Center [Amsterdam], National Heart, Lung and Blood Institute, Osong Health Technology Administration Complex, University of Pennsylvania, Department of Genetics, University of North Carolina at Chapel Hill (UNC), Loyola University [Chicago], Centre Hospitalier Universitaire Vaudois (CHUV), Hudson Alpha Institute for Biotechnology, Erasmus University Rotterdam, Department of Medical Sciences, Uppsala University, Università degli Studi di Milano [Milano] (UNIMI), Istituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Université Paris-Sud - Paris 11 (UP11), Azienda Sanitaria Firenze, Wellcome Trust Genome Campus, The Wellcome Trust Sanger Institute [Cambridge], University of Lincoln, University of Washington [Seattle], Amgen Inc., The University of Texas Health Science Center at Houston (UTHealth), VU University Amsterdam, University of Dresden Medical School, Université de Lausanne (UNIL), Healthcare NHS Trust, National Health Research Institutes, National University Health System [Singapore] (NUHS), Duke-NUS Medical School [Singapore], Singapore Eye Research Institute [Singapore] (SERI), National Human Genome Research Institute (NHGRI), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Radiology and nuclear medicine, EMGO - Mental health, Lin, Li, Mach, François, ProdInra, Migration, University of Oxford, Università degli studi di Verona = University of Verona (UNIVR), University of Copenhagen = Københavns Universitet (UCPH), Università degli Studi di Milano = University of Milan (UNIMI), Vrije Universiteit Amsterdam [Amsterdam] (VU), Université de Lausanne = University of Lausanne (UNIL), Institut National de la Recherche Agronomique (INRA)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris Descartes - Paris 5 (UPD5)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratoire d'Informatique Médicale et Ingénierie des Connaissances en e-Santé (LIMICS), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Université Sorbonne Paris Nord, Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU), EMGO+ - Lifestyle, Overweight and Diabetes, Biological Psychology, APH - Amsterdam Public Health, Epidemiology and Data Science, Graduate School, Other departments, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, Luan, Jian'an [0000-0003-3137-6337], Barroso, Ines [0000-0001-5800-4520], Danesh, John [0000-0003-1158-6791], Khaw, Kay-Tee [0000-0002-8802-2903], Markus, Hugh [0000-0002-9794-5996], Ong, Kenneth [0000-0003-4689-7530], Johnson, Kathleen [0000-0002-6823-3252], Wareham, Nicholas [0000-0003-1422-2993], Zhao, Jing Hua [0000-0003-4930-3582], Langenberg, Claudia [0000-0002-5017-7344], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), CHARGE-EchoGen Consortium, CHARGE-HF Consortium, Wellcome Trust Case Control Consortium, Medical Microbiology & Infectious Diseases, Epidemiology, Neurology, Radiology & Nuclear Medicine, Internal Medicine, Clinical Genetics, Biochemistry, National Institute for Health Research, and Medical Research Council (MRC)
Subjects: 0301 basic medicine, Netherlands Twin Register (NTR), CHROMATIN, [SDV]Life Sciences [q-bio], LOCI, Genome-wide association study, Blood Pressure, SUSCEPTIBILITY, Bioinformatics, Cardiovascular, Genome-wide association studies, Medical and Health Sciences, single nucleotide polymorphism, CHARGE-EchoGen consortium, GWAS, 2.1 Biological and endogenous factors, Aetiology, Cells, Cultured, African Continental Ancestry Group, Genetics & Heredity, Genetics, ddc:616, Kidney, Framingham Risk Score, Cultured, COMMON VARIANTS, 11 Medical And Health Sciences, Single Nucleotide, Biological Sciences, African Continental Ancestry Group/genetics, Asian Continental Ancestry Group/genetics, Blood Pressure/genetics, Genome-Wide Association Study, Humans, Hypertension/genetics, Hypertension/pathology, Microarray Analysis, Polymorphism, Single Nucleotide, [SDV] Life Sciences [q-bio], medicine.anatomical_structure, Hypertension/genetics/pathology, Hypertension, Medical genetics, Wellcome Trust Case Control Consortium, Life Sciences & Biomedicine, TRAITS, Biotechnology, Asian Continental Ancestry Group, medicine.medical_specialty, CHARGE-EchoGen Consortium, Cells, Black People, BIOLOGY, Single-nucleotide polymorphism, Biology, Blood pressure, hypertension, genetics, single nucleotide polymorphism, GWAS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Asian People, medicine, Polymorphism, GENOME-WIDE ASSOCIATION, CELL-TYPES, METAANALYSIS, Genetic association, Science & Technology, CHARGE-HF consortium, 06 Biological Sciences, Genetic architecture, 030104 developmental biology, Blood pressure, CHARGE-HF Consortium, ARTERIAL-HYPERTENSION, Developmental Biology
Abstract: To dissect the genetic architecture of blood pressure (BP) and assess how its elevation promotes downstream cardiovascular diseases, we analyzed 128,272 SNPs from targeted and genome-wide arrays in 201,529 individuals of European ancestry. Genotypes from an additional 140,886 individuals of European ancestry were used as validation for loci reaching genome-wide significance but without prior support in the literature. We identified 66 BP loci, of which 17 were novel and 15 harbored multiple distinct association signals, and which together explain up to 3.5% of BP variation. The 66 index SNPs were enriched for cis-regulatory elements, particularly in vascular endothelial cells, consistent with a primary role in BP control through modulating blood vessel tone and fluid filtration across multiple tissues, not solely the kidney. Importantly, the 66 index SNPs combined in a risk score showed comparable effects in 64,421 individuals of non-European descent (South-Asian, East-Asian and African), confirming that these are ancestral physiological effects that arose prior to human migration out of Africa. The 66-SNP BP risk score was significantly associated with target-organ damage in multiple tissues, with minor effects in the kidney. Our data expand current knowledge of BP pathways, and also, highlight that BP regulation and its effects may occur in multiple organs and tissues beyond the classic renal system.
Published: 2016
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31. Gene-age interactions in blood pressure regulation: a large-scale investigation with the CHARGE, Global BPgen, and ICBP Consortia

Author: Shih-Jen Hwang, Siim Sõber, Peng Chen, Albert Hofman, Daniel I. Chasman, Toby Johnson, Cornelia M. van Duijn, Mika Kähönen, Abbas Dehghan, Bruce M. Psaty, Niek Verweij, Chiea Chuen Khor, Jian'an Luan, Gavin Lucas, Daniel Levy, Jianjun Liu, Kenneth Rice, Kiang Liu, Fernando Rivadeneira, Ruth J. F. Loos, Rainer Rettig, Robert A. Scott, Henry Völzke, Paul M. Ridker, Gudny Eiriksdottir, Harold Snieder, Dabeeru C. Rao, Tin Aung, Leo-Pekka Lyytikäinen, Terri L. Young, Eric J.G. Sijbrands, Tamara B. Harris, Rudolf A. de Boer, Germaine C. Verwoert, Andrew D. Johnson, Ramachandran S. Vasan, Yik Ying Teo, Dhananjay Vaidya, Xiuqing Guo, Tanguy Corre, Alan James, Myriam Fornage, Aravinda Chakravarti, Rick Twee-Hee Ong, Melanie M. van der Klauw, Jerome I. Rotter, Oscar H. Franco, Ching-Yu Cheng, Gemma Cadby, Carla Lluis-Ganella, Edward G. Lakatta, Najaf Amin, Lenore J. Launer, Lyle J. Palmer, Hugh Watkins, Jennifer L. Bragg-Gresham, Serena Sanna, Brenda W.J.H. Penninx, Leslie J. Raffel, George J. Papanicolau, Tien Yin Wong, Maris Laan, Alanna C. Morrison, Kay-Tee Khaw, Zoltán Kutalik, Jacqueline C.M. Witteman, Martin G. Larson, Gang Shi, Anuj Goel, Pierre Meneton, Peter J. van der Most, Eranga N. Vithana, Xiangjun Gu, Jeannette Simino, Ronald P. Stolk, David S. Siscovick, Joshua C. Bis, Serge Hercberg, Claude Bouchard, Walter Palmas, Jing Hua Zhao, Vilmundur Gudnason, Eric Boerwinkle, Catharina A. Hartman, Guo Li, Murielle Bochud, Gerjan Navis, Christian Gieger, Uwe Völker, Xueling Sim, Pim van der Harst, Roberto Elosua, Terho Lehtimäki, E. Shyong Tai, Olli T. Raitakari, Nicholas J. Wareham, Lynda M. Rose, Martin Farrall, Albert V. Smith, Cisca Wijmenga, Ilja M. Nolte, André G. Uitterlinden, Georg Ehret, Ehret, Georg Benedikt, Bochud, Murielle, Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Lifestyle Medicine (LM), Vascular Ageing Programme (VAP), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), EMGO+ - Mental Health, Internal Medicine, Epidemiology, Public Health, Erasmus MC other, Obstetrics & Gynecology, Psychiatry, EMGO - Mental health, Washington University in Saint Louis (WUSTL), University of Washington [Seattle], Brigham and Women's Hospital [Boston], Hôpitaux Universitaires de Genève (HUG), Johns Hopkins University (JHU), University of Texas, Harbor UCLA Medical Center [Torrance, Ca.], National Heart, Lung, and Blood Institute [Bethesda] (NHLBI), National Heart, Lung and Blood Institute, Partenaires INRAE, Erasmus University Rotterdam, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, University of Iceland, University of Michigan [Ann Arbor], University of Michigan System, Ontario Institute for Cancer Research, University of Western Australia, Samuel Lunenfeld Research Institute, Saw Swee Hock School of Public Health, National University of Singapore (NUS), National University Health System [Singapore] (NUHS), Singapore Eye Research Institute [Singapore] (SERI), Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Department of Medical Genetics, University of Groningen, University of Oxford [Oxford], Queen Mary University of London (QMUL), Genome Institute of Singapore (GIS), Hospital del Mar Medical Research Institute, Institute of metabolic Science, MRC Epidemiology Unit, Addenbrooke's Hospital, Fimlab Laboratories, University of Tampere, Centre for Molecular Epidemiology, University of Tartu, Human Genomics Laboratory, Pennington Biomedical Research Center, Louisiana State University (LSU)-Louisiana State University (LSU), CIBER de Epidemiología y Salud Pública (CIBERESP), German Research Center for Environmental Health - Helmholtz Center München (GmbH), Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, National Institutes of Health, Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Sir Charles Gairdner Hospital, School of Medicine and Pharmacology, The University of Western Australia (UWA), Institute of Public Health, Department of Public Health and Primary Care, University of Cambridge [UK] (CAM), Department of Mathematics, Boston University [Boston] (BU), Northwestern University [Evanston], VU University Amsterdam, Leiden University, Group Health Cooperative, Medical Genetics Institute, Cedars-Sinai Medical Center, Department of Clinical Physiology and Nuclear Medicine, Aarhus University Hospital, Research Centre of Applied and Preventive Cardiovascular Medicine, University of Turku, Department of Biostatistics [Oslo], Institute of Basic Medical Sciences [Oslo], Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO)-Faculty of Medicine [Oslo], University of Oslo (UiO)-University of Oslo (UiO), Consiglio Nazionale delle Ricerche (CNR), Netherlands Consortium for Healthy Aging, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, Institute for Community Medicine, Duke University [Durham], Medtronic, Amgen, and Vrije universiteit = Free university of Amsterdam [Amsterdam] (VU)
Subjects: Aging, [SDV]Life Sciences [q-bio], Genome-wide association study, Blood Pressure, 030204 cardiovascular system & hematology, VARIANTS, Medical and Health Sciences, Cohort Studies, 0302 clinical medicine, 2.1 Biological and endogenous factors, Genetics(clinical), Aetiology, ENVIRONMENT INTERACTIONS, Genetics (clinical), POPULATION, Genetics, Genetics & Heredity, ddc:616, 0303 health sciences, education.field_of_study, Age Factors, WOMEN, Biological Sciences, Middle Aged, CROHNS-DISEASE, CARDIOVASCULAR-DISEASE, Main effect, Adult, Adolescent, SUSCEPTIBILITY LOCI, Population, Locus (genetics), Single-nucleotide polymorphism, Biology, Article, 03 medical and health sciences, Young Adult, Clinical Research, SNP, Humans, GENOME-WIDE ASSOCIATION, education, METAANALYSIS, 030304 developmental biology, Genetic association, Aged, HYPERTENSION, ta1184, Human Genome, ta3121, Blood pressure, LifeLines Cohort Study
Abstract: Although age-dependent effects on blood pressure (BP) have been reported, they have not been systematically investigated in large-scale genome-wide association studies (GWASs). We leveraged the infrastructure of three well-established consortia (CHARGE, GBPgen, and ICBP) and a nonstandard approach (age stratification and metaregression) to conduct a genome-wide search of common variants with age-dependent effects on systolic (SBP), diastolic (DBP), mean arterial (MAP), and pulse (PP) pressure. In a two-staged design using 99,241 individuals of European ancestry, we identified 20 genome-wide significant (p≤ 5 10) loci by using joint tests of the SNP main effect and SNP-age interaction. Nine of the significant loci demonstrated nominal evidence of age-dependent effects on BP by tests of the interactions alone. Index SNPs in the EHBP1L1 (DBP and MAP), CASZ1 (SBP and MAP), and GOSR2 (PP) loci exhibited the largest age interactions, with opposite directions of effect in the young versus the old. The changes in the genetic effects over time were small but nonnegligible (up to 1.58 mm Hg over 60 years). The EHBP1L1 locus was discovered through gene-age interactions only in whites but had DBP main effects replicated (p = 8.3 10) in 8,682 Asians from Singapore, indicating potential interethnic heterogeneity. A secondary analysis revealed 22 loci with evidence of age-specific effects (e.g., only in 20 to 29-year-olds). Age can be used to select samples with larger genetic effect sizes and more homogenous phenotypes, which may increase statistical power. Age-dependent effects identified through novel statistical approaches can provide insight into the biology and temporal regulation underlying BP associations. © 2014 The American Society of Human Genetics.
Published: 2014
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32. Obesity and the microvasculature: A systematic review and meta-analysis

Author: Barbara E.K. Klein, Aljoscha Steffen Neubauer, Paul Mitchell, Sébastien Czernichow, Mohammad Kamran Ikram, Ronald Klein, Sophia Zoungas, Bamini Gopinath, Seang-Mei Saw, Adrien Boillot, Jie Jin Wang, Tien Yin Wong, Serge Hercberg, E. Shyong Tai, Caroline C W Klaver, Laima Brazionis, Université Paris Diderot - Paris 7 (UPD7), Hôpital Ambroise Paré [AP-HP], George Institute for Global Health, The University of Sydney, Westmead Institute for Medical Research, Partenaires INRAE, University of Wisconsin-Madison, Saw Swee Hock School of Public Health, National University of Singapore (NUS), Erasmus University Rotterdam, Singapore Eye Research Institute, Department of Medicine, University of Melbourne-Royal Melbourne Hospital, Ludwig Maximilians University of Munich, Unité de Recherche en Epidémiologie Nutritionnelle (UREN), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), PRES Sorbonne Paris Cité, Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Centre de recherche en épidémiologie et santé des populations (CESP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), National Health and Medical Research Council [124317, 396414, 209057], National Heart Foundation, Centre for Clinical Research Excellence in Clinical Science in Diabetes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Sorbonne Paris Cité (USPC)-Université Paris 13 (UP13)-Conservatoire National des Arts et Métiers [CNAM] (CNAM)-Institut National de la Recherche Agronomique (INRA), ProdInra, Migration, Ludwig-Maximilians University [Munich] (LMU), Université Paris 13 (UP13)-Institut National de la Recherche Agronomique (INRA)-Conservatoire National des Arts et Métiers [CNAM] (CNAM), HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-HESAM Université - Communauté d'universités et d'établissements Hautes écoles Sorbonne Arts et métiers université (HESAM)-Université Sorbonne Paris Cité (USPC)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM), Ophthalmology, and Obstetrics & Gynecology
Subjects: Pathology, Epidemiology, [SDV]Life Sciences [q-bio], 030204 cardiovascular system & hematology, Overweight, Cardiovascular, Body Mass Index, 0302 clinical medicine, Risk Factors, maladie cardiovasculaire, Child, Prospective cohort study, 2. Zero hunger, Multidisciplinary, indice de masse corporelle, Diabetic retinopathy, Middle Aged, 3. Good health, [SDV] Life Sciences [q-bio], obésité, Meta-analysis, 030220 oncology & carcinogenesis, Cardiology, Retinal Disorders, Medicine, medicine.symptom, Research Article, Adult, medicine.medical_specialty, Systematic Reviews, Adolescent, Clinical Research Design, Science, Childhood obesity, 03 medical and health sciences, SDG 3 - Good Health and Well-being, Vascular Biology, Internal medicine, medicine, Humans, Obesity, Cardiovascular Disease Epidemiology, Nutrition, Aged, business.industry, Retinal Vessels, surpoids, medicine.disease, Ophthalmology, Intima-media thickness, Microvessels, 030221 ophthalmology & optometry, Meta-Analyses, Metabolic syndrome, business, Body mass index, 030217 neurology & neurosurgery
Abstract: International audience; Background: Overweight and obesity are thought to significantly influence a person's risk of cardiovascular disease, possibly via its effect on the microvasculature. Retinal vascular caliber is a surrogate marker of microvascular disease and a predictor of cardiovascular events. The aim of this systematic review and meta-analysis was to determine the association between body mass index (BMI) and retinal vascular caliber. Methods and Findings: Relevant studies were identified by searches of the MEDLINE and EMBASE databases from 1966 to August 2011. Standardized forms were used for data extraction. Among over 44,000 individuals, obese subjects had narrower arteriolar and wider venular calibers when compared with normal weight subjects, independent of conventional cardiovascular risk factors. In adults, a 1 kg/m(2) increase in BMI was associated with a difference of 0.07 mm [95% CI: -0.08; -0.06] in arteriolar caliber and 0.22 mu m [95% CI: 0.21; 0.23] in venular caliber. Similar results were found for children. Conclusions: Higher BMI is associated with narrower retinal arteriolar and wider venular calibers. Further prospective studies are needed to examine whether a causative relationship between BMI and retinal microcirculation exists.
Published: 2013
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33. Genetic modifiers of menopausal hormone replacement therapy and breast cancer risk: A genome-wide interaction study

Author: Florence Menegaux, Gord Glendon, Graham G. Giles, Penny Webb, Kamila Czene, Jean Wang, Irene L. Andrulis, Per Hall, Melissa C. Southey, Emilie Cordina-Duverger, Jonine D. Figueroa, Julia A. Knight, Jenny Chang-Claude, Alan Ashworth, Janet E. Olson, Fergus J. Couch, Manjeet K. Bolla, Gianluca Severi, Nick Orr, Thérèse Truong, Anna Marie Mulligan, Volker Harth, Pascal Guénel, Lars Beckmann, Hatef Darabi, Laura Baglietto, Dieter Flesch-Janys, Hiltrud Brauch, Hugues Aschard, Jianjun Liu, Georgia Chenevix-Trench, David J. Hunter, Sabine Behrens, Keith Humpreys, Minouk J. Schoemaker, Montserrat Garcia-Closas, Thomas Brüning, Celine M. Vachon, Peter Kraft, Anja Rudolph, Kristen N. Stevens, Sara Lindström, Anthony J. Swerdlow, Heli Nevanlinna, Jolanta Lissowska, Rebecca Hein, Douglas F. Easton, Mikael Eriksson, Stephen J. Chanock, Program in Genetic Epidemiology and Statistical Genetics (PGESG - BOSTON), Harvard School of Public Health, Division of Cancer Epidemiology, German Cancer Research Center - Deutsches Krebsforschungszentrum [Heidelberg] (DKFZ), Saw Swee Hock School of Public Health, National University of Singapore (NUS), Cancer Research UK Cambridge Institute [Cambridge, Royaume-Uni] (CRUK), University of Cambridge [UK] (CAM), Centre de recherche en épidémiologie et santé des populations (CESP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris-Sud - Paris 11 (UP11)-Hôpital Paul Brousse-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)
Subjects: Oncology, Cancer Research, Endocrinology, Diabetes and Metabolism, Genome-wide association study, Bioinformatics, 0302 clinical medicine, Breast cancer, Endocrinology, MESH: Carcinoma, Lobular, MESH: Risk Factors, Polymorphism (computer science), Risk Factors, Genome-wide, Modifier, [STAT.AP]Statistics [stat]/Applications [stat.AP], 0303 health sciences, Tumor, MESH: Polymorphism, Single Nucleotide, MESH: Hormone Replacement Therapy, MESH: Genetic Predisposition to Disease, Single Nucleotide, Prognosis, MESH: Case-Control Studies, Diabetes and Metabolism, 030220 oncology & carcinogenesis, MESH: Genes, Modifier, Female, MESH: Biomarkers, Tumor, [STAT.ME]Statistics [stat]/Methodology [stat.ME], Menopausal hormone therapy, medicine.medical_specialty, Hormone Replacement Therapy, Single-nucleotide polymorphism, Breast Neoplasms, Biology, Polymorphism, Single Nucleotide, MESH: Prognosis, Article, Lobular, 03 medical and health sciences, Meta-Analysis as Topic, Internal medicine, Biomarkers, Tumor, medicine, SNP, Humans, MESH: Meta-Analysis as Topic, Genetic Predisposition to Disease, Genetic variation, Polymorphism, 030304 developmental biology, Genetic association, MESH: Humans, Genes, Modifier, Haplotype, Carcinoma, Case-control study, medicine.disease, Carcinoma, Lobular, [SDV.GEN.GH]Life Sciences [q-bio]/Genetics/Human genetics, Genes, Case-Control Studies, Genome-Wide Association Study, MESH: Genome-Wide Association Study, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, [INFO.INFO-BI]Computer Science [cs]/Bioinformatics [q-bio.QM], MESH: Female, MESH: Breast Neoplasms, Biomarkers
Abstract: Women using menopausal hormone therapy (MHT) are at increased risk of developing breast cancer (BC). To detect genetic modifiers of the association between current use of MHT and BC risk, we conducted a meta-analysis of four genome-wide case-only studies followed by replication in 11 case–control studies. We used a case-only design to assess interactions between single-nucleotide polymorphisms (SNPs) and current MHT use on risk of overall and lobular BC. The discovery stage included 2920 cases (541 lobular) from four genome-wide association studies. The top 1391 SNPs showingPvalues for interaction (Pint) −3were selected for replication using pooled case–control data from 11 studies of the Breast Cancer Association Consortium, including 7689 cases (676 lobular) and 9266 controls. Fixed-effects meta-analysis was used to derive combinedPint. No SNP reached genome-wide significance in either the discovery or combined stage. We observed effect modification of current MHT use on overall BC risk by two SNPs on chr13 nearPOMP(combinedPint≤8.9×10−6), two SNPs inSLC25A21(combinedPint≤4.8×10−5), and three SNPs inPLCG2(combinedPint≤4.5×10−5). The association between lobular BC risk was potentially modified by one SNP inTMEFF2(combinedPint≤2.7×10−5), one SNP inCD80(combinedPint≤8.2×10−6), three SNPs on chr17 nearTMEM132E(combinedPint≤2.2×10−6), and two SNPs on chr18 nearSLC25A52(combinedPint≤4.6×10−5). In conclusion, polymorphisms in genes related to solute transportation in mitochondria, transmembrane signaling, and immune cell activation are potentially modifying BC risk associated with current use of MHT. These findings warrant replication in independent studies.
Published: 2013
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34. Roles and Dynamics within Community Mental Health Systems During the COVID-19 Pandemic: A Qualitative Systematic Review and Meta-Ethnography.

Author: Sim CSL, Asharani PV, Subramaniam M, and Yi H
Subjects: Humans, Anthropology, Cultural, Mental Health, Qualitative Research, COVID-19 epidemiology
Abstract: Globally, COVID-19 had an immense impact on mental health systems, but research on how community mental health (CMH) systems and services contributed to the pandemic mental health response is limited. We conducted a systematic review and meta-ethnography to understand the roles of CMH services, determinants of the quality of CMH care, and dynamics within CMH systems during COVID-19. We searched and screened across five databases and appraised study quality using the CASP tool, which yielded 27 qualitative studies. Our meta-ethnographic process used Noblit and Hare's approach for synthesizing findings and applying interpretive analysis to original research. This identified several key themes. Firstly, CMH systems played the valuable pandemic role of safety nets and networks for the broader mental health ecosystem, while CMH service providers offered a continuous relationship of trust to service users amidst pandemic disruptions. Secondly, we found that the determinants of quality CMH care during COVID-19 included resourcing and capacity, connections across service providers, customized care options, ease of access, and human connection. Finally, we observed that power dynamics across the CMH landscape disproportionately excluded marginalized groups from mainstream CMH systems and services. Our findings suggest that while the pandemic role of CMH was clear, effectiveness was driven by the efforts of individual service providers to meet demand and service users' needs. To reprise its pandemic role in the future, a concerted effort is needed to make CMH systems a valuable part of countries' disaster mental health response and to invest in quality care, particularly for marginalized groups.
Published: 2024
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35. Trends of early-onset colorectal cancer in Singapore: an epidemiological study of a multi-ethnic population.

Author: Chen HLR, Chong QD, Tay B, Zhou S, Wong EYT, Seow-En I, Tan KK, Wang Y, Seow A, Tan KE, Tan BHI, and Tan SH
Abstract: Background: Colorectal cancer (CRC) incidence and mortality in those aged 50 years and above have decreased over the last 2 decades. However, there is a rising incidence in CRC among individuals under 50 years of age, termed early-onset colorectal cancer (EOCRC). EOCRC patients are more advanced stage at diagnosis and may suffer more psychosocial, emotional and financial distress., Objective: Our study examines the epidemiological shifts of CRC in Singapore, a multiethnic country., Methods: CRCs diagnosed at age 20 and above from 1968 to 2019 were identified from the Singapore Cancer Registry. Patient characteristics included gender, ethnicity and age of diagnosis of CRC. Population information was obtained from the Department of Statistics Singapore. Age specific incidence rates (ASR) and age standardized incidence rates (ASIR) were calculated. The cohort was divided into 3 age groups: 20 - 49, 50 - 64 and ≥65 years. Temporal trends of incidence rates were modelled with Joinpoint Regression. Birth cohort models were fitted using the National Cancer Institute (NCI) age-period-cohort analysis tool. Cancer-specific survival analysis was performed with Cox proportional hazards model., Results: 53044 CRCs were included, and 6183 (11.7%) adults aged 20 to 49 years were diagnosed with EOCRC. ASR of EOCRC rose from 5 in 1968 to 9 per 100,000 in 1996 at 2.1% annually and rose to 10 per 100,000 in 2019 at 0.64% annually. The ASR for CRC among adults 50 to 64 years rose at 3% annually from 1968 to 1987 and plateaued from 1987 while the ASR for adults aged 65 and above rose at 4.1% from 1968 to 1989 and 1.3% annually from 1989 to 2003 but decreased from 2003 onwards at 1% annually. There is a continued rise in the ASR of EOCRC among males (APC: 1.5%) compared to females (APC: 0.41%) and a significant increase in APC for early-onset rectal cancer at 1.5% yearly. Compared to the 1950 - 1954 birth reference cohort, the 1970 - 1984 birth cohort had a significantly higher incidence rate ratio (IRR) of 1.17 - 1.36 for rectal cancer while there was no significant change for colon cancer in later cohorts. There were differences in CRC trends across the 3 ethnic groups. Malays had a rapid and persistent rise in ASR of CRC across all age groups (APC: 2- 3%) while amongst young Chinese, only the ASR of rectal cancer is increasing (APC: 1.5%). EOCRC patients had better survival compared to patients diagnosed at 65 years and above (HR 0.73, 95% CI 0.67 - 0.79, P <0.001) after adjusting for covariates., Conclusions: The rise in incidence of rectal cancer among young adults especially among Chinese and Malays in Singapore highlights the need for further research to diagnose CRC earlier and reduce cancer-related morbidity and mortality.
Published: 2024
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36. Theory-based behaviour modification of Asian adults with type-2 diabetes mellitus after participating in a novel telemonitoring system: a qualitative research study.

Author: Tan NC, Gong PP, Lee CS, Goh SKL, Ang SB, and Koh GCH
Subjects: Humans, Male, Female, Middle Aged, Singapore, Adult, Self Efficacy, Aged, Health Behavior, Asian People, Blood Glucose analysis, Blood Glucose metabolism, Blood Glucose Self-Monitoring, Blood Pressure, Diabetes Mellitus, Type 2 therapy, Qualitative Research, Telemedicine
Abstract: Objective: Telemonitoring (TM) remotely monitors individuals' health. Awareness of personal clinical data has resulted in improved glycaemic control in adults with type-2 diabetes mellitus (T2DM). However, its effects on their health-seeking behaviour remain unclear. This study aims to explore and understand the effects of a multicomponent TM system on self-efficacy in adults with T2DM., Design: A qualitative study using semistructured interviews., Setting: A public primary care clinic which is located at an estate in north-eastern Singapore with a population of about 300 000 multiethnic Asian residents., Participants: 21 participants who completed 6 months of TM intervention which included immediate feedback on glucose and blood pressure readings, educational videos on exercise and nutrition, and personalised support with TM nurse when clinical parameters met high glucose or blood pressure thresholds., Results: The health belief model was used to explain the participants' behaviour change, including (1) immediate feedback from TM clinical parameters (blood pressure and glucose), raised their awareness of their health status and disease control to motivate behaviour change; (2) notification of higher glucose through TM allowed patients to reflect on their recent food consumption and nudged them to select healthier food options; (3) App teleeducation improved health literacy and supported lifestyle changes; (4) cues for action through personalised engagement with TM nurse and via automated reminders and (5) the TM system enhanced self-efficacy by modifying their multifaceted self-care behaviours., Conclusion: TM heightened understanding among adults with T2DM of their potential for health complications and increased awareness of the benefits of proper diabetes management. It also helped lower the barriers to self-management and further enhanced their self-efficacy in self-care. The system and care team provided users with cues for health which was perceived to lead to adapting their lifestyle in order to achieve better health outcomes., Clinical Trials Registration Number: NCT04306770., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2024
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37. Decision-making for childhood vaccination in crisis settings: a survey of practice & barriers.

Author: Light PM, Singh NS, Alhaffar M, Allison LE, Mounier-Jack S, Ratnayake R, Checchi F, and Abdelmagid N
Abstract: Background: Children, particularly those who have received no routine vaccinations (zero-dose children), are at high risk of vaccine-preventable diseases in humanitarian crisis settings. However, the decision-making processes underlying vaccine intervention design and delivery in such settings are poorly understood. The present study investigated the decision-making practices of organisations involved in childhood vaccination in humanitarian crisis settings globally via an online survey., Methods: Individuals involved in the design or delivery of childhood vaccination programmes in humanitarian crisis settings were invited to fill out a self-administered online survey. Respondents were asked about factors influencing intervention design and vaccine delivery; use of technical guidance, specifically the WHO decision-making framework for vaccination in acute humanitarian emergencies (WHO Framework); and practices for reaching zero-dose children., Results: Fourteen responses were received. Large international organisations and UN agencies were overrepresented in the sample. Technical guidance was considered of high importance when designing vaccine interventions. However, the WHO Framework is not available in relevant languages and has not been well-distributed to local and national actors. Awareness of initiatives to reach zero-dose children was high within our sample, though this may not accurately reflect global awareness. Security and resource availability were key barriers to vaccine delivery and reaching zero-dose children. Problems with vaccine access in our sample pertained primarily to issues with the procurement system rather than vaccine cost., Conclusions: The WHO Framework should be provided in more languages, and vaccination actors at local and national level should be engaged to improve its practicality and increase awareness of its aims. In order to reach zero-dose children, vaccines must be made available for use in expanded age groups, which is sometimes not currently feasible within the Gavi/UNICEF procurement system. Clarifying this policy would allow relevant organisations to reach more zero-dose children. Additionally, security is a key barrier impeding vaccine delivery, including for zero-dose children. Safe operational space for humanitarian actors in conflict must be maintained and global conflict resolution mechanisms improved., Competing Interests: Declarations. Ethics approval and consent to participate: Ethics approval for this study was provided by the London School of Hygiene and Tropical Medicine Ethics Committee, ref. 27604. Consent for publication: Please see additional files 1 and 2. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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38. Retinal thickness predicts the risk of cognitive decline over five years.

Author: Eppenberger LS, Li C, Wong D, Tan B, Garhöfer G, Hilal S, Chong E, Toh AQ, Venketasubramanian N, Chen CL, Schmetterer L, and Chua J
Subjects: Humans, Male, Female, Aged, Middle Aged, Neuropsychological Tests, Cohort Studies, Risk Factors, Retinal Ganglion Cells pathology, Cognitive Dysfunction diagnostic imaging, Tomography, Optical Coherence methods, Retina diagnostic imaging, Retina pathology
Abstract: Background: Dementia poses a significant burden on healthcare systems. Early identification of individuals at risk for cognitive decline is crucial. The retina, an extension of the central nervous system, reflects neurodegenerative changes. Optical coherence tomography (OCT) is a non-invasive tool for assessing retinal health and has shown promise in predicting cognitive decline. However, prior studies produced mixed results., Methods: This study investigated a large cohort (n = 490) of Asian individuals attending memory clinics. Participants underwent comprehensive neuropsychological testing annually for five years. Retinal thickness was measured by OCT at baseline. We assessed the association between baseline retinal thickness and subsequent cognitive decline., Results: Participants with a significantly thinner macular ganglion cell-inner plexiform layer (GCIPL) at baseline (≤ 79 μm) had a 38% greater risk of cognitive decline compared to those who did not (≥ 88 μm; p = 0.037). In a multivariable model accounting for age, education, cerebrovascular disease status, hypertension, hyperlipidemia, diabetes and smoking, thinner GCIPL was associated with an increased risk of cognitive decline (hazard ratio = 1.14, 95% CI = 1.01-1.30, p = 0.035). Retinal nerve fiber layer (RNFL) thickness was not associated with cognitive decline., Conclusions: This study suggests that OCT-derived macular GCIPL thickness may be a valuable biomarker for identifying individuals at risk of cognitive decline. Our findings highlight GCIPL as a potentially more sensitive marker compared to RNFL thickness for detecting early neurodegenerative changes., Trial Registration Number and Name of the Trial Registry: National Healthcare Group Domain-Specific Review Board (NHG DSRB) reference numbers DSRB Ref: 2018/01368. Name of the trial: Harmonisation project., Competing Interests: Declarations. Ethics approval and consent to participate: This study was approved by the National Healthcare Group Domain-Specific Review Board (NHG DSRB reference number 2018/01098 and 2010/00017). The study adhered to the tenets of the Declaration of Helsinki and its later amendments. Study coordinators obtained written informed consent from all participants or legal representatives before their study inclusion. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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39. Reproductive factors and risk of epithelial ovarian cancer: results from the Asia Cohort Consortium.

Author: Merritt MA, Abe SK, Islam MR, Rahman MS, Saito E, Katagiri R, Shin A, Choi JY, Le Marchand L, Killeen JL, Gao YT, Tamakoshi A, Koh WP, Sakata R, Sawada N, Tsuji I, Sugawara Y, Kim J, Park SK, Kweon SS, Shu XO, Kimura T, Yuan JM, Tsugane S, Kanemura S, Lu Y, Shin MH, Wen W, Ahsan H, Boffetta P, Chia KS, Matsuo K, Qiao YL, Rothman N, Zheng W, Inoue M, and Kang D
Abstract: Background: There are scarce data on risk factors for epithelial ovarian cancer (EOC) in Asian populations. Our goal was to advance knowledge on reproductive -related risk factors for EOC in a large population of Asian women., Methods: This study used pooled individual data from baseline questionnaires in 11 prospective cohorts (baseline years, 1958-2015) in the Asia Cohort Consortium. A Cox proportional hazards regression model was used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) adjusting for age, parity and cohort., Results: After a mean = 17.0 years (SD = 6.3) of follow-up, 674 incident invasive EOC cases were identified among 325,626 women. In multivariable adjusted models we observed an inverse association with parity (5+ children vs. 0, HR = 0.44, 95% CI = 0.28-0.68, Ptrend < 0.001), and a positive association with increasing menopausal age (55+ years vs. <45, HR = 1.77, 95% CI = 1.05-3.01, Ptrend = 0.02) for risk of all EOC., Conclusions: In this large study of Asian women we identified an inverse association with parity and a positive association with higher menopausal age in relation to EOC risk. Further work is needed to understand EOC risk factors for rare histologic subtypes that occur more frequently in Asian populations., Competing Interests: Competing interests: The authors declare no competing interests. Ethics approval and consent to participate: The institutional review board of the National Cancer Center Japan approved the analysis in the Asia Cohort Consortium (ACC) (number 2014-041) and each cohort study included in ACC received ethical approval by their respective institutional ethical committees. Written or oral consent was provided by all subjects who participated in the study. The authors certify that the study was performed in accordance with the ethical standards as laid down in the 1964 Declaration of Helsinki and its later amendments. Consent for publication: This is an observational study involving the analysis of secondary data only. All data were deidentified. There was no direct interaction with human subjects for this study., (© 2024. The Author(s).)
Published: 2024
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40. Meta-analysis of Face Perception in Schizophrenia Spectrum Disorders: Evidence for Differential Impairment in Emotion Face Perception.

Author: Mewton P, Dawel A, Miller EJ, Shou Y, and Christensen BK
Subjects: Humans, Cognitive Dysfunction physiopathology, Cognitive Dysfunction etiology, Facial Expression, Social Perception, Psychotic Disorders physiopathology, Facial Recognition physiology, Schizophrenia physiopathology, Emotions physiology
Abstract: Background and Hypothesis: Schizophrenia spectrum disorders (SSD) are associated with face perception impairments. It is unclear whether impairments are equal across aspects of face perception or larger-indicating a differential impairment-for perceiving emotions relative to other characteristics (eg, identity, age). While many studies have attempted to compare emotion and non-emotion face perception in SSD, they have varied in design and produced conflicting findings. Additionally, prior meta-analyses on this topic were not designed to disentangle differential emotion impairments from broader impairments in face perception or cognition. We hypothesize that SSD-related impairments are larger for emotion than non-emotion face perception, but study characteristics moderate this differential impairment., Study Design: We meta-analyzed 313 effect sizes from 104 articles to investigate if SSD-related impairments are significantly greater for emotion than non-emotion face perception. We tested whether key study characteristics moderated these impairments, including SSD severity, sample intelligence matching, task difficulty, and task memory dependency., Study Results: We found significantly greater impairments for emotion (Cohen's d = 0.74) than non-emotion face perception (d = 0.55) in SSD relative to control samples, regardless of SSD severity, intelligence matching, or task difficulty. Importantly, this effect was obscured when non-emotion tasks used a memory-dependent design., Conclusions: This is the first meta-analysis to demonstrate a differential emotion impairment in SSD that cannot be explained by broader impairments in face perception or cognition. The findings also underscore the critical role of task matching in studies of face perception impairments; to prevent confounding influences from memory-dependent task designs., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Maryland Psychiatric Research Center.)
Published: 2024
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41. Healthcare utilisation patterns and contributory factors among middle-aged adults: a scoping review.

Author: Ng Y, Low AJA, Chan C, Lim YL, Lee CE, Tan HK, and Ng QX
Subjects: Humans, Middle Aged, Health Behavior, Multimorbidity, Socioeconomic Factors, Patient Acceptance of Health Care statistics & numerical data
Abstract: Background: Middle-aged adults, defined as individuals between the ages of 45 and 64, represent a significant yet under researched group of healthcare service users. This scoping review aimed to provide a comprehensive overview of the patterns of healthcare utilisation and the factors contributing to them within this demographic., Methods: Following PRISMA-ScR guidelines and the framework proposed by Arksey and O'Malley, a systematic literature search was conducted across PubMed, EMBASE, and the Cochrane Library databases from their inception until July 2023. Key search terms such as "healthcare utilisation" and "middle-aged" were used to identify relevant studies. Articles were included if they were original cohort, case-control, or cross-sectional studies published in English. The findings were then synthesised narratively, by identifying recurring concepts and grouping them into broader themes. The themes were categorised according to the Andersen healthcare utilisation model's three factors: predisposing factors, enabling factors, and need-related factors., Results: After screening 4,810 records, a total of 25 articles were selected for final analysis, comprising 15 from developed countries and 10 from developing countries. Consistent factors influencing healthcare utilisation included multimorbidity, socioeconomic status, and poor health behaviours. Differences emerged across contexts: in developed countries, healthcare utilisation was influenced by lifestyle behaviours and access to private care, while in developing countries, socioeconomic inequalities and limited insurance coverage played more dominant roles. Healthcare system structures likely shaped utilisation patterns., Conclusion: Healthcare utilisation among middle-aged adults is driven by an interplay of medical, social, and economic factors that vary across contexts. Common contributors, such as multimorbidity and poor health behaviours, highlight the need for targeted interventions and policies focusing on primary and preventive care to address the long-term burden of healthcare utilisation. This demographic faces unique challenges in managing healthcare decisions amidst varying systemic and individual-level challenges, which should be further studied., Competing Interests: Declarations. Ethics approval and consent to participate: Not applicable. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests., (© 2024. The Author(s).)
Published: 2024
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42. Diet, physical activity, and sleep in relation to postprandial glucose responses under free-living conditions: an intensive longitudinal observational study.

Author: Yao J, Brugger VK, Edney SM, Tai ES, Sim X, Müller-Riemenschneider F, and van Dam RM
Subjects: Humans, Male, Female, Middle Aged, Adult, Longitudinal Studies, Aged, Singapore, Young Adult, Life Style, Postprandial Period, Sleep physiology, Blood Glucose metabolism, Exercise physiology, Diet methods
Abstract: Background: It remains unclear what lifestyle behaviors are optimal for controlling postprandial glucose responses under real-world circumstances in persons without diabetes. We aimed to assess associations of diet, physical activity, and sleep with postprandial glucose responses in Asian adults without diabetes under free-living conditions., Methods: We conducted an observational study collecting intensive longitudinal data using smartphone-based ecological momentary assessments, accelerometers, and continuous glucose monitors over nine free-living days in Singaporean men and women aged 21-69 years without diabetes. The outcome was the 2-h postprandial glucose incremental area under the curve (mmol/l*min). Associations were estimated using linear mixed-effect models., Results: The analyses included 11,333 meals in 789 participants. Greater variations in glucose and lifestyle measures were observed within individuals than between individuals. Higher consumption of carbohydrate-rich and deep-fried foods and lower consumption of protein-rich foods were significantly associated with higher postprandial glucose levels (incremental area under the curve). The strongest association was observed for including refined grains (46.2 [95% CI: 40.3, 52.1]) in meals. Longer postprandial light-intensity physical activity (-24.7 [(-39.5, -9.9] per h) and moderate-to-vigorous-intensity physical activity (-58.0 [-73.8, -42.3]) were associated with substantially lower postprandial glucose levels. Longer daily light-intensity physical activity (-7.5 [-10.7, -4.2]) and sleep duration (-2.7 [-4.4, -1.0]) were also associated with lower postprandial glucose levels. Furthermore, postprandial glucose levels were the lowest in the morning and the highest in the afternoon. The results were largely consistent for males and females and for participants with and without prediabetes., Conclusions: Consuming less refined grains and more protein-rich foods, getting more physical activity (particularly during the postprandial period), and having a longer sleep duration were associated with lower postprandial glucose levels in Asian adults without diabetes. Our findings support multi-component lifestyle modifications for postprandial glucose control and highlight the importance of the timing of eating and physical activity., Competing Interests: Declarations. Ethics approval and consent to participate: All participants provided informed consent. Ethical approval was obtained from the Institutional Review Board of the National University of Singapore (NUS ref: NUS-IRB-2020-50). Consent for publication: Not applicable. Competing interests: No potential conflicts of interest relevant to this article were reported., (© 2024. The Author(s).)
Published: 2024
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43. The spanish and catalan versions of the kidney patient reported experience measure (PREM) for chronic kidney disease (CKD): cultural adaptation and face validity.

Author: Moharra M, Llupià A, Bayés B, Almazán C, Busby A, and Herdman M
Subjects: Humans, Male, Female, Spain, Reproducibility of Results, Middle Aged, Surveys and Questionnaires, Adult, Aged, Language, Renal Insufficiency, Chronic therapy, Patient Reported Outcome Measures, Translations
Abstract: Background: Chronic kidney disease (CKD) is a progressive condition affecting more than 800 million individuals worldwide. Patient Reported Experience Measures (PREMs) are questionnaires aimed at evaluating patients' experiences with healthcare received. Given that CKD management often involves continuous treatments, capturing patient experiences can guide improvements in care that align with patients' preferences, making PREMS a relevant tool in CKD management. The Kidney PREM questionnaire was developed in the United Kingdom to measure patient experience across entire service provisions in patients with chronic kidney disease (CKD). This study aimed to adapt the English version to Spanish and Catalan and assess the face validity of the new language versions., Methods: The translation process was guided by the International Society of Pharmacoeconomics and Outcome Research (ISPOR) Principles of Good Practice for the Translation and Cultural Adaptation of Patient‑Reported Outcomes Measures and included forward and back translation, cognitive debriefing, and harmonisation between the Spanish and Catalan versions. Face validity was assessed in a sample of Spanish- and Catalan-speaking health professionals., Results: In the cognitive debriefing, 9 patients with CKD (4 in Catalan and 5 in Spanish) participated. Fourteen healthcare professionals (2 nurses and 12 nephrologists) assessed the face validity of the Catalan and Spanish versions. Overall, the language used in the original version of the questionnaire did not cause substantial problems for translation into Catalan or Spanish. Patients generally found the questionnaire to be relevant and relatively easy to complete but reported some difficulties with questionnaire design, including the use of 'skip' questions. Clinicians and nurses highly rated the questionnaire in terms of relevance (mean score of 8.7 on a 0-10 scale) and acceptability, indicating good face validity, but considered some elements to be lacking, such as the absence of an open-ended question or any queries regarding lifestyle., Conclusions: It was feasible to produce culturally adapted Spanish and Catalan versions of the Kidney PREM questionnaire, and they showed acceptable face validity. They will be useful tools for furthering research and clinical practice in CKD patients in Spain., Competing Interests: Declarations. Ethics approval and consent to participate: The questionnaire did not involve any invasive procedure or data collection beyond standard clinical practices. Therefore, ethical approval from an ethics committee was deemed unnecessary according to “Law 14/2007 of July 3 on Biomedical Research”. All participants gave fully informed written consent to participate. Consent to publish: Not applicable. Conflict of interest: The authors report no conflicts of interest., (© 2024. The Author(s).)
Published: 2024
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44. Risk of mortality in Fusobacterium species bloodstream infection from a large Australian cohort.

Author: Stewart AG, Edwards F, Harris PNA, Paterson DL, and Laupland KB
Abstract: Background: Fusobacterium species are anaerobic Gram-negative bacilli which are uncommon causes of bloodstream infection (BSI). This genus commonly colonises the gastrointestinal tract and can result in significant morbidity., Methods: All blood cultures with growth of Fusobacterium species among residents of Queensland, Australia (population ≈ 5 million) were retrospectively identified over a 20-year period. Clinical, microbiological and outcome information was obtained from state-wide databases., Results: 377 incident Fusobacterium species BSI among 375 individuals for an age and sex-standardised incidence of 4.4 per million residents per year. Median age was 47 years (IQR, 24.9-65.8) and 156 (42%) incident episodes were in females. There was a bimodal frequency distribution with respect to age with peaks occurring around 20 and 65 years, respectively. The most identified source of infection was the abdominal (17%), followed by head and neck (12%). 8% of patients had a septic thrombus present, and 4% had an abscess associated with their BSI. Most isolates were F. nucleatum (142, 38%) and F. necrophorum (140, 37%). 9% of isolates were resistant to penicillin. Older age (aHR 1.02, 95% CI 1.01-1.05), healthcare-associated hospital onset (aHR 3.16, 95% CI 1.35-7.40), and Charlson Comorbidity index (aHR 1.20, 95% CI 1.06-1.35) were all associated with 30-day all cause case-fatality. Oropharyngeal source appeared to be a protective factor (P = 0.02)., Conclusions: Fusobacterium species BSI results in significant morbidity and can cause death in vulnerable patient groups such as the elderly and those with malignancy. An identifiable oropharyngeal source identifies a favourable host., Competing Interests: Declarations. Ethical approval: The Human Research Ethics Committee (HREC) at Royal Brisbane and Women’s Hospital approved this study and granted a waiver of individual consent (LNR/2020/QRBW/62494). Consent to participate: Not applicable. Consent for publication: Not applicable. Conflict of interest: DLP has received research grants from Merck, Pfizer, bioMerieux and Shionogi outside of the submitted work. He has also received personal fees from AMR Action Fund, Merck, Pfizer, Shionogi, Spero, Lysovant, The Medicines Company, Entasis, VenatoRx, QPex, bioMerieux and Accelerate and is conducting a study on E. coli vaccination sponsored by Janssen. PNAH has received research grants from Merck, Sharpe and Dohme (MSD), Sandoz and Shionogi Ltd, outside of the submitted work, and has served on advisory boards for OpGen, Merck and Sandoz and received speakers fees from Pfizer, OpGen and Sandoz paid to the University of Queensland. All other authors: none to declare., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Published: 2024
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45. Sustainable antimicrobial resistance surveillance: time for a global funding mechanism.

Author: Painter C, Limmathurotsakul D, Roberts T, van Doorn HR, Mayxay M, Lubell Y, Day NPJ, Turner P, and Ashley EA
Abstract: Antimicrobial resistance (AMR) is predicted to outstrip malaria, HIV, and tuberculosis combined as the leading infectious cause of death by 2050. Strengthening the knowledge and evidence base for AMR with surveillance and research is one of the five main objectives of the WHO Global Action Plan on AMR. While recent efforts to strengthen diagnosis and surveillance have been encouraging, these are unlikely to be sustainable without continued funding support in most low-resource settings. We estimated the continued costs of a standard national AMR surveillance system in low-income and middle-income countries (LMICs). For 46 LMICs, the costs would account for more than 2% of their total domestic general government health expenditure (GGHE-D), and for 28 of these countries, the costs are more than 5% of their total GGHE-D. This high cost is not sustainable without a long-term global financing mechanism., Competing Interests: Declaration of interests The funding source was not involved in the development of this manuscript. We declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)
Published: 2024
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46. Hepatitis B Virus Exposure, Seroprotection Status, and Susceptibility in Health Care Workers From Lao People's Democratic Republic: Cross-Sectional Study.

Author: Virachith S, Phakhounthong K, Khounvisith V, Mayxay M, Kounnavong S, Sayasone S, Hübschen JM, and Black AP
Subjects: Humans, Laos epidemiology, Male, Middle Aged, Female, Adult, Cross-Sectional Studies, Aged, Young Adult, Hepatitis B virus immunology, Prevalence, Disease Susceptibility, Occupational Exposure statistics & numerical data, Occupational Exposure adverse effects, Southeast Asian People, Health Personnel statistics & numerical data, Hepatitis B epidemiology, Hepatitis B prevention & control
Abstract: Background: Despite the high prevalence of chronic hepatitis B virus (HBV) infection in adults in Lao People's Democratic Republic (Lao PDR), Lao health care workers (HCWs) have previously been shown to have low levels of protection against infection. Furthermore, the prevalence of hepatitis D virus (HDV), which increases disease severity in individuals infected with HBV, is not known in Lao PDR., Objective: This study aimed to estimate the exposure and seroprotection against HBV, as well as exposure to HDV, in Lao HCWs from 5 provinces., Methods: In 2020, a total of 666 HCWs aged 20 to 65 years from 5 provinces of Lao PDR were recruited, and their sera were tested by enzyme-linked immunosorbent assay to determine their HBV and HDV coinfection status., Results: HBV exposure, as indicated by the presence of anti-hepatitis B core antibodies, was 40.1% (267/666) overall and significantly higher for HCWs from Oudomxay province (21/31, 67.7%; adjusted odds ratio 3.69, 95% CI 1.68-8.12; P=.001). The prevalence of hepatitis B surface antigen was 5.4% (36/666) overall and increased with age, from 3.6% (9/248) in those aged ≤30 years to 6.8% (8/118) in those aged ≥50 years. Only 28.7% (191/666) of participants had serological indication of immunization. We could find no evidence for HDV exposure in this study., Conclusions: The study found intermediate hepatitis B surface antigen prevalence among HCWs in Lao PDR, with no evidence of HDV coinfection. Notably, a significant proportion of HCWs remains susceptible to HBV, indicating a substantial gap in seroprotection against the disease., (© Siriphone Virachith, Khanxayaphone Phakhounthong, Vilaysone Khounvisith, Mayfong Mayxay, Sengchanh Kounnavong, Somphou Sayasone, Judith M Hübschen, Antony P Black. Originally published in JMIR Public Health and Surveillance (https://publichealth.jmir.org).)
Published: 2024
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47. A systematic review of environmental covariates and methods for spatial or temporal scrub typhus distribution prediction.

Author: Wang Q, Ma T, Ding FY, Lim A, Takaya S, Saraswati K, Hao MM, Jiang D, Fang LQ, Sartorius B, Day NPJ, and Maude RJ
Subjects: Humans, Spatio-Temporal Analysis, Risk Factors, Environment, Scrub Typhus epidemiology
Abstract: Background: Scrub typhus is underdiagnosed and underreported but emerging as a global public health problem. To inform future burden and prediction studies we examined through a systematic review the potential effect of environmental covariates on scrub typhus occurrence and the methods which have been used for its prediction., Methods: In this systematic review, we searched PubMed, Scopus, Web of Science, China National Knowledge Infrastructure and other databases, with no language and publication time restrictions, for studies that investigated environmental covariates or utilized methods to predict the spatial or temporal human. Data were manually extracted following a set of queries and systematic analysis was conducted., Results: We included 68 articles published in 1978-2024 with relevant data from 7 countries/regions. Significant environmental risk factors for scrub typhus include temperature (showing positive or inverted-U relationships), precipitation (with positive or inverted-U patterns), humidity (exhibiting complex positive, inverted-U, or W-shaped associations), sunshine duration (with positive, inverted-U associations), elevation, the normalized difference vegetation index (NDVI), and the proportion of cropland. Socioeconomic and biological factors were rarely explored. Autoregressive Integrated Moving Average (ARIMA) (n = 8) and ecological niche modelling (ENM) approach (n = 11) were the most popular methods for predicting temporal trends and spatial distribution of scrub typhus, respectively., Conclusions: Our findings summarized the evidence on environmental covariates affecting scrub typhus occurrence and the methodologies used for predictive modelling. We review the existing knowledge gaps and outline recommendations for future studies modelling disease prediction and burden., Trial Registration: PROSPERO CRD42022315209., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:Qian Wang reports financial support was provided by Wellcome Trust. Fangyu Ding reports financial support was provided by National Natural Science Foundation of China. Fangyu Ding reports financial support was provided by Chinese Academy of Sciences Youth Innovation Promotion Association. Kartika Saraswati reports financial support was provided by NRF International Partnership Funding Initiative. If there are other authors, they declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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48. Clinical and proteomic profiles of chronic kidney disease in heart failure with reduced and preserved ejection fraction.

Author: Voordes GHD, Voors AA, Hoegl A, Madsen CT, van Essen BJ, Ouwerkerk W, Tromp J, de la Rambelje MA, Grønborg M, Refsgaard JC, Lang CC, Barascuk-Michaelsen N, and Damman K
Subjects: Humans, Male, Female, Aged, Middle Aged, Cohort Studies, Aged, 80 and over, Scotland epidemiology, Heart Failure physiopathology, Heart Failure blood, Stroke Volume physiology, Renal Insufficiency, Chronic physiopathology, Renal Insufficiency, Chronic blood, Renal Insufficiency, Chronic epidemiology, Renal Insufficiency, Chronic diagnosis, Proteomics methods
Abstract: Background: Chronic kidney disease (CKD) is prevalent and related to poor clinical outcomes in patients with heart failure (HF). The pathophysiology of CKD in HF with a reduced ejection fraction (HFrEF) and HF with a preserved ejection fraction (HFpEF) is not well defined. In this study we compared clinical and proteomic profiles of CKD between patients with HFrEF and HFpEF., Methods: We included 478 patients of the Scottish BIOSTAT-CHF cohort, of which 246 had HFrEF and 232 had HFpEF. CKD was defined as an eGFR <60 mL/min/1.73m 2 . We compared HFrEF-patients with CKD to HFpEF-patients with CKD using logistic- and Cox-regression. We performed a differential expression analysis using 6376 proteins., Results: The prevalence of CKD was 36 % and 32 % in patients with HFpEF and HFrEF, respectively. CKD patients were on average 7 years older. BMI, higher NT-proBNP, ACE-inhibitors, HDL-cholesterol and Stroke were associated with CKD- patients with HFrEF. In HFpEF, CKD was associated with MRA-use and higher platelet count. CKD was associated with increased risk of death or heart failure hospitalization (HR 1.82, p < 0.001), with similar effect in HFrEF and HFpEF. The pattern of differentially expressed proteins between patients with and without CKD was similar in both HF-groups., Conclusion: Clinical profiles related to CKD- patients with HFrEF were different from CKD-patients with HFrEF. CKD was associated with an increased risk of death or heart failure hospitalization, which was not different between HFpEF and HFrEF. Patterns of circulating proteins were similar between CKD-patients with HFpEF and HFrEF, suggesting no major differences in CKD-pathophysiology., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Published: 2024
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49. Proxy medical decision-making: national survey.

Author: Phua AI, Zakaria C, Pakianathan PV, Chan N, Lim MJR, Liew TM, Koh GCH, and Foong PS
Abstract: Objectives: Population ageing and increased care needs lead to adults making consequential medical decisions for others, potentially impacting treatment and end of life. We aim to describe the prevalence of medical decision-making by proxy among the national population and associated demographic and care factors., Methods: We designed a cross-sectional online survey with a nationally representative adult cohort with an 80% participation rate. 311 Singapore residents completed the survey., Results: 73% of respondents reported having ever assisted others with medical decisions, while 58% have ever assisted with activities of daily living (ADLs), and 88% with instrumental ADLs (IADLs). Having a digital caregiver account, having a lasting power of attorney as a donee and assisting with ADLs and IADLs are significantly associated with proxy medical decision-making. Gender, ethnicity, income and age did not appear to have a significant impact., Conclusions: A majority of Singapore adults assist others with caregiving tasks and medical decision-making. These helping behaviours are often performed informally, which may increase decisional burden for caregivers and potential abuse of power., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)
Published: 2024
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50. Biomarkers of PUFA and cardiovascular risk factors and events in healthy Asian populations: a systematic review.

Author: Lee YQ, Tan KH, and Chong MF
Subjects: Humans, Fatty Acids, Omega-6 blood, Asia, Risk Factors, Vascular Stiffness, Biomarkers blood, Cardiovascular Diseases blood, Heart Disease Risk Factors, Fatty Acids, Omega-3 blood, Asian People
Abstract: The associations between circulating PUFA and cardiovascular risk factors and events in healthy Asian populations have been less examined robustly compared with Western populations. This systematic review aimed to summarise current evidence on the associations between n -3 and n -6 PUFA biomarkers and cardiovascular risk factors and events in healthy Asian populations. Four databases were searched for observational studies from 2010 until 2024. Twenty-three studies were eligible, which covered six Asian countries and included events ( n 7), traditional risk factors such as blood pressure and lipids ( n 4), physical signs such as arterial stiffness ( n 4), non-traditional lipid markers ( n 1), markers of inflammation ( n 4), markers of thrombosis ( n 2) and non-invasive imaging-based markers ( n 5). Biological sample types included plasma ( n 6), serum ( n 14) and erythrocyte ( n 3). Higher circulating total n -3 PUFA appeared to be associated with lower hypertension risk and specifically EPA and DHA to be associated with lower myocardial infarction risk, reduction in TAG and inflammation. Higher circulating linoleic acid was associated with improved lipid profiles and lower inflammation. Limited evidence led to inconclusive associations between circulating n -6 PUFA biomarkers and CVD events and blood pressure. No consistent associations with arterial stiffness, obesity, thrombosis and imaging-based biomarkers were observed for circulating PUFA biomarkers in Asian populations. Limited studies exist for each outcome; hence, results should be interpreted with caution. More high-quality and prospective studies in Asian populations are warranted. Several recommendations such as sample size justification and reporting of non-respondents rate are proposed for future studies.
Published: 2024
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