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1. Environmental factors associated with biological use and surgery in inflammatory bowel disease

Author: Michiel Voskuil, Paul Geertsema, Behrooz Z. Alizadeh, Kimberley W. J. van der Sloot, Eleonora A. M. Festen, Marijn C. Visschedijk, Hendrik M. van Dullemen, Gerard Dijkstra, Hanneke C Rijkmans, Rinse K. Weersma, Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Translational Immunology Groningen (TRIGR), and Groningen Institute for Organ Transplantation (GIOT)
Subjects: Male, Disease, Logistic regression, PHENOTYPE, Inflammatory bowel disease, Biological Factors, 0302 clinical medicine, Crohn Disease, Floors and Floorcoverings, Surveys and Questionnaires, Epidemiology, EPIDEMIOLOGY, Gastroenterology, Beer, Shift Work Schedule, Middle Aged, Ulcerative colitis, CROHNS-DISEASE, Natural history, Exposome, Clinical Gastroenterology, 030220 oncology & carcinogenesis, 030211 gastroenterology & hepatology, Female, SMOKING, Adult, Risk, Toothbrushing, medicine.medical_specialty, lifestyle, IBD, EXERCISE, APPENDECTOMY, Cigarette Smoking, 03 medical and health sciences, Groningen IBD Environmental Questionnaire, environmental factors, ACTIVE DISEASE, medicine, Humans, Cannabis, Hepatology, business.industry, NATURAL-HISTORY, medicine.disease, SLEEP, Surgery, Etiology, RISK-FACTORS, Colitis, Ulcerative, Smoking Cessation, business, Regular Articles, clinical intestinal disorders
Abstract: Background and Aim: While major efforts were made studying the complex etiology of inflammatory bowel disease (IBD) including environmental factors, less is known about underlying causes leading to the heterogeneous and highly variable course of disease. As cigarette smoking cessation is the best-known environmental factor with beneficial effect in Crohn's disease (CD), more exposome factors are likely involved. Further insights into the role of the exposome in heterogeneity of disease might not only further knowledge of underlying pathways, but also allow for better risk stratification. Methods: Seven hundred twenty-eight IBD patients completed the validated Groningen IBD Environmental Questionnaire, collecting exposome data for 93 exposome factors. Associations with disease course, that is, for need for surgery or biological therapy, were evaluated using univariate and multivariate-adjusted logistic regression modeling. Results: No significant associations were seen after Bonferroni correction. However, 11 novel exposome factors were identified with P
Published: 2021

2. Genome-wide association study of circulating interleukin 6 levels identifies novel loci

Author: Martina Müller-Nurasyid, Jerome I. Rotter, David M. Evans, John P. Kemp, Emelia J. Benjamin, Graciela E. Delgado, Vilmundur Gudnason, Ann Hammarstedt, Panos Deloukas, Aroon D. Hingorani, Riccardo E. Marioni, David Stacey, Jenny van Dongen, Eric Boerwinkle, Joachim Heinrich, Yongmei Liu, S. Goya Wannamethee, Delilah Zabaneh, Braxton D. Mitchell, Marie Standl, Jackie F. Price, Maria G. Stathopoulou, Yoav Ben-Shlomo, Joris Deelen, Eero Kajantie, Mohammadreza Abdollahi, Christie M. Ballantyne, Johan G. Eriksson, Ilkka Seppälä, Elnaz Naderi, Barbara J. Jefferis, Richard W Morris, Nicholas J. Timpson, George Dedoussis, Sirpa Jalkanen, Mika Kivimäki, Perminder S. Sachdev, Diana van Heemst, Melanie Waldenberger, Gaurav Singhal, Elisabeth Thiering, Olli T. Raitakari, Anders Hamsten, Zoltán Kutalik, L. Bain, Eco J. C. de Geus, Tarunveer S. Ahluwalia, Yuri Milaneschi, Hubert Scharnagl, Juan P. Casas, Georg Homuth, Claes Ohlsson, Abbas Dehghan, Nicola J. Armstrong, Behrooz Z. Alizadeh, Terho Lehtimäki, Steve E. Humphries, Naveed Sattar, Bram P. Prins, Peter Rossing, Sophie Visvikis-Siest, Joana A. Revez, Ilja M. Nolte, Stella Trompet, Harold Snieder, Marian Beekman, Diana Marek, Beate St Pourcain, Thorkild I. A. Sørensen, Silvia Naitza, Karen A. Mather, Uwe Völker, Eline Slagboom, Tina Shah, Magdalene C. Jawahar, Jens Baumert, Alexander Teumer, Dorret I. Boomsma, Marcus E. Kleber, Peter Vollenweider, Wolfgang Koenig, Brenda W.J.H. Penninx, Kenneth Rice, Ian J. Deary, Pedro Marques-Vidal, Donna K. Arnett, Eleonora Porcu, Jouke-Jan Hottenga, Maria Sabater-Lleal, Bruce M. Psaty, Matthias Nauck, Dan Mellström, Joel Eriksson, Bernhard T. Baune, Debbie A Lawlor, Catherine Toben, Peter H. Whincup, Toshiko Tanaka, Stavroula Kanoni, Katri Räikkönen, Gonneke Willemsen, Bengt Sennblad, Julian N. Trollor, Yalda Jamshidi, Sarah E. Harris, Jari Lahti, Joshua C. Bis, Peter Durda, Yen Pei C. Chang, Jorgen Engmann, Tom R. Gaunt, Stella Aslibekyan, Anbupalam Thalamuthu, Mary F. Feitosa, Angela Silveira, Tine Jess, Stela McLachlan, J. Wouter Jukema, Chen Lu, Simon P. Mooijaart, Tim D. Spector, Harald Grallert, Winfried März, Alexandros M. Petrelis, Manuel A. R. Ferreira, Meena Kumari, Stochastics, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Methodology, CHARGE Inflammation Working Group, Epidemiology, Tampere University, Department of Clinical Chemistry, Clinical Medicine, Steno Diabetes Center, University of Copenhagen = Københavns Universitet (KU), University of Groningen [Groningen], Murdoch University, University of Alabama at Birmingham [ Birmingham] (UAB), QIMR Berghofer Medical Research Institute, University College of London [London] (UCL), Helmholtz-Zentrum München (HZM), Leiden University Medical Center (LUMC), University of Bristol [Bristol], University of Washington [Seattle], University of Maryland School of Medicine, University of Maryland System, Vrije Universiteit Amsterdam [Amsterdam] (VU), VU University Medical Center [Amsterdam], University of Heidelberg, Medical Faculty, Swiss Institute of Bioinformatics [Lausanne] (SIB), Université de Lausanne (UNIL), Sahlgrenska Academy at University of Gothenburg [Göteborg], National Institute for Health and Welfare [Helsinki], University of Helsinki, William Harvey Research Institute, Barts and the London Medical School, University of Queensland [Brisbane], School of Public Health [Boston], Boston University [Boston] (BU), MRC Institute of Genetics and Molecular Medicine [Edinburgh] (IGMM), University of Edinburgh-Medical Research Council, University of Edinburgh, Amsterdam UMC, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), Istituto di Ricerca Genetica e Biomedica (IRGB), Consiglio Nazionale delle Ricerche [Roma] (CNR), Karolinska Institutet [Stockholm], University of Tampere [Finland], Adelaide Medical School [Australia], University of Adelaide, Universität Greifswald - University of Greifswald, University of New South Wales [Sydney] (UNSW), Prince of Wales Hospital, Ludwig-Maximilians-Universität München (LMU), Baylor College of Medicine (BCM), Baylor University, Boston University School of Medicine (BUSM), VA Boston Healthcare System, Harokopio University of Athens, Max planck Institute for Biology of Ageing [Cologne], Larner College of Medicine [University of Vermont, Burlington], University of Vermont [Burlington], Washington University School of Medicine in St. Louis, Washington University in Saint Louis (WUSTL), Interfaculty Institute for Genetics and Functional Genomics, Ernst-Moritz-Arndt-Universität Greifswald, University of Turku, St George's, University of London, Statens Serum Institut [Copenhagen], Medical Faculty [Mannheim], Wake Forest School of Medicine [Winston-Salem], Wake Forest Baptist Medical Center, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Johannes Gutenberg - Universität Mainz (JGU), Vrije Universiteit Medical Centre (VUMC), British Heart Foundation Glasgow Cardiovascular Research Centre (BHF GCRC), University of Glasgow-NHS Greater Glasgow and Clyde, Medical University Graz, Uppsala Universitet [Uppsala], Max Planck Institute for Psycholinguistics, Max-Planck-Gesellschaft, Donders Institute for Brain, Cognition and Behaviour, Radboud university [Nijmegen], University of Kentucky, Melbourne Medical School [Melbourne], Faculty of Medicine, Dentistry and Health Sciences [Melbourne], University of Melbourne-University of Melbourne, University Hospital Münster - Universitaetsklinikum Muenster [Germany] (UKM), University of Maryland [Baltimore], Queen Mary University of London (QMUL), University of Iceland [Reykjavik], Ludwig Maximilian University [Munich] (LMU), Melbourne School of Population and Global Health [Melbourne], University of Melbourne, Deutsches Herzzentrum München (DHM), German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), University of Ulm (UUlm), University of Essex, Greifswald University Hospital, Novo Nordisk Foundation Center for Basic Metabolic Research (CBMR), Faculty of Health and Medical Sciences, University of Copenhagen = Københavns Universitet (KU)-University of Copenhagen = Københavns Universitet (KU), King‘s College London, University of Cambridge [UK] (CAM), Harbor UCLA Medical Center [Torrance, Ca.], Erasmus University Medical Center [Rotterdam] (Erasmus MC), University of Texas Health Science Center, The University of Texas Health Science Center at Houston (UTHealth), Human Genome Sequencing Center [Houston] (HGSC), Baylor University-Baylor University, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Digital Health, HUS Children and Adolescents, Lastentautien yksikkö, Children's Hospital, Clinicum, Department of Bacteriology and Immunology, Department of Public Health, Department of Psychology and Logopedics, Research Programs Unit, Johan Eriksson / Principal Investigator, Department of General Practice and Primary Health Care, Doctoral Programme in Human Behaviour, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: AcademicSubjects/SCI01140, [SDV]Life Sciences [q-bio], Genome-wide association study, 030204 cardiovascular system & hematology, DISEASE, Pathogenesis, Cohort Studies, 0302 clinical medicine, cytokine, SYSTEMIC-LUPUS-ERYTHEMATOSUS, Association Studies Article, ComputingMilieux_MISCELLANEOUS, Genetics (clinical), Genetics, 0303 health sciences, ARCHITECTURE, CHRONIC INFLAMMATION, 1184 Genetics, developmental biology, physiology, General Medicine, RECEPTOR IL-6R GENE, C-REACTIVE PROTEIN, hla-drb1 gene, 3. Good health, Medical genetics, Medical Genetics, chromosomes, medicine.medical_specialty, SUSCEPTIBILITY LOCI, European Continental Ancestry Group, Locus (genetics), Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, anti-inflammatory agents, White People, 03 medical and health sciences, medicine, Humans, Genetic Predisposition to Disease, Interleukin 6, Molecular Biology, Medicinsk genetik, 030304 developmental biology, PRODUCE IL-6, Interleukin-6, Chromosome, Receptors, Interleukin-6, RHEUMATOID-ARTHRITIS, Interleukin 1 Receptor Antagonist Protein, Gene Expression Regulation, Genetic Loci, CELLS, biology.protein, 1182 Biochemistry, cell and molecular biology, Human genome, 3111 Biomedicine, Genome-Wide Association Study, HLA-DRB1 Chains, Interleukin-1
Abstract: Interleukin 6 (IL-6) is a multifunctional cytokine with both pro- and anti-inflammatory properties with a heritability estimate of up to 61%. The circulating levels of IL-6 in blood have been associated with an increased risk of complex disease pathogenesis. We conducted a two-staged, discovery and replication meta genome-wide association study (GWAS) of circulating serum IL-6 levels comprising up to 67 428 (ndiscovery = 52 654 and nreplication = 14 774) individuals of European ancestry. The inverse variance fixed effects based discovery meta-analysis, followed by replication led to the identification of two independent loci, IL1F10/IL1RN rs6734238 on chromosome (Chr) 2q14, (Pcombined = 1.8 × 10−11), HLA-DRB1/DRB5 rs660895 on Chr6p21 (Pcombined = 1.5 × 10−10) in the combined meta-analyses of all samples. We also replicated the IL6R rs4537545 locus on Chr1q21 (Pcombined = 1.2 × 10−122). Our study identifies novel loci for circulating IL-6 levels uncovering new immunological and inflammatory pathways that may influence IL-6 pathobiology.
Published: 2021

3. Tacrolimus and mycophenolate mofetil as second-line treatment in autoimmune hepatitis

Author: Mohammad-Hossein Somi, Neda Khalilian Ekrami, Behrooz Z. Alizadeh, Morteza Ghojazadeh, Mohammadreza Abdollahi, H. Marike Boezen, Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: medicine.medical_specialty, Efficacy, Azathioprine, Autoimmune hepatitis, Second-line, Mycophenolate, DIAGNOSIS, THERAPY, Tacrolimus, Grading of Recommendations Assessment, INTOLERANT, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, medicine, MANAGEMENT, Humans, Adverse effect, business.industry, Mortality rate, Gastroenterology, General Medicine, Mycophenolic Acid, medicine.disease, Confidence interval, Hepatitis, Autoimmune, Meta-analysis, Treatment Outcome, GRADE, Grading of Recommendations Assessment, Development and Evaluation approach, 030220 oncology & carcinogenesis, Systematic review, UPDATE, 030211 gastroenterology & hepatology, business, CONSENSUS, Immunosuppressive Agents, Development and Evaluation approach, medicine.drug
Abstract: BACKGROUNDThe standard management of autoimmune hepatitis (AIH) is based on corticosteroids, alone or in combination with azathioprine. Second-line treatments are needed for patients who have refractory disease. However, high-quality data on the alternative management of AIH are scarce.AIMTo evaluate the efficacy and safety of tacrolimus and mycophenolate mofetil (MMF) and the quality of evidence by using the Grading of Recommendations Assessment, Development and Evaluation approach (GRADE).METHODSA systematic review and meta-analysis of the available data were performed. We calculated pooled event rates for three outcome measures: Biochemical remission, adverse events, and mortality, with their corresponding 95% confidence intervals (CI).RESULTSThe pooled biochemical remission rate was 68.9% (95%CI: 60.4-76.2) for tacrolimus, and 59.6% (95%CI: 54.8-64.2) for MMF, and rates of adverse events were 25.5% (95%CI: 12.4-45.3) for tacrolimus and 24.1% (95%CI: 15.4-35.7) for MMF. The pooled mortality rate was estimated at 11.5% (95%CI: 7.1-18.1) for tacrolimus and 9.01% (95%CI: 6.2-12.8) for MMF. Pooled biochemical remission rates for tacrolimus and MMF in patients with intolerance to standard therapy were 56.6% (CI: 43.4-56.6) vs 73.5% (CI: 58.1-84.7), and among non-responders were 59.1% (CI: 48.7-68.8) vs 40.8% (CI: 32.3-50.0), respectively. Moreover, the overall quality assessments using GRADE proved to be very low for all our outcomes in both treatment groups.CONCLUSIONTacrolimus and MMF are in practice considered effective for patients with AIH who are non-responders or intolerant to first-line treatment, but we found no high-quality evidence to support this statement.
Published: 2020

4. Diet quality indices and gastrointestinal cancer risk: results from the Lifelines study

Author: Sara Moazzen, Behrooz Z. Alizadeh, Francisco O Cortes-Ibañez, Geertruida H. de Bock, Bert van der Vegt, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE)
Subjects: Risk, medicine.medical_specialty, Gastrointestinal Neoplasms/epidemiology, CARCINOMA, Colorectal cancer, ESOPHAGEAL CANCER, Population, Stomach neoplasms, Medicine (miscellaneous), Colorectal neoplasms, Cohort Studies, ADHERENCE, PREVENTION GUIDELINES, Interquartile range, Risk Factors, Internal medicine, GASTRIC ADENOCARCINOMA, medicine, Humans, Gastrointestinal cancer, Prospective Studies, education, Colorectal Neoplasms/epidemiology, Proportional Hazards Models, education.field_of_study, Nutrition and Dietetics, business.industry, Nutrition quality, MORTALITY, Hazard ratio, Cancer, Original Contribution, ASSOCIATION, medicine.disease, Gastrointestinal neoplasms, Diet, Oesophageal neoplasms, MEDITERRANEAN DIET, PHYSICAL-ACTIVITY, Diet quality, Cohort, NUTRITION, business
Abstract: Objective To investigate the long-term association between four dietary quality indices and the risk of gastrointestinal (GI) cancer. Methods Baseline details of the dietary intake of participants, assessed by a single food frequency questionnaire from the prospective Lifelines population-based cohort were translated to diet quality scores using several dietary and dietary-lifestyle indices. Incident cases of GI cancer were then assessed by linkage to the Dutch nationwide histo-cytopathology registry. The association between GI cancer risk and diet quality (defined as higher quintiles on dietary indices compared to the first quintile) was assessed by multivariable Cox proportional hazard models. Results We included 72,695 participants aged 51.20 ± 8.71 years with a median follow-up to cancer diagnosis of 8 years (interquartile range 2 years). During follow-up, 434 colorectal cancers and 139 upper GI cancers were diagnosed. There was a significant reduction in colorectal cancer risk for high categories in the American Cancer Society (ACS) Index (hazard ratio 0.62; 95% CI 0.46–0.84). However, high dietary index scores were not associated with strong beneficial effects on upper GI cancer risk. Conclusion High quintiles on the ACS Index were associated with a significantly reduced risk of colorectal cancer. This index may be of use in a colorectal cancer prevention program.
Published: 2022

5. Identification of Environmental Risk Factors Associated With the Development of Inflammatory Bowel Disease

Author: Kimberley W. J. van der Sloot, Behrooz Z. Alizadeh, Rinse K. Weersma, Gerard Dijkstra, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Translational Immunology Groningen (TRIGR), Groningen Institute for Organ Transplantation (GIOT), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Adult, Male, Exposome, medicine.medical_specialty, Disease, Inflammatory bowel disease, Cohort Studies, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Surveys and Questionnaires, Internal medicine, Odds Ratio, Humans, Medicine, 030212 general & internal medicine, Irritable bowel syndrome, business.industry, Gastroenterology, Environmental Exposure, General Medicine, Middle Aged, Inflammatory Bowel Diseases, medicine.disease, Ulcerative colitis, Logistic Models, Case-Control Studies, Cohort, Etiology, Female, 030211 gastroenterology & hepatology, business, Cohort study
Abstract: Background and AimsMultiple genetic and environmental factors are involved in the aetiology of inflammatory bowel disease [IBD] including Crohn’s disease [CD] and ulcerative colitis [UC], but data on these exposome factors are difficult to identify. Several exposome factors such as smoking have been shown to be involved; as for other environmental factors, eg stress, results have been conflicting.MethodsWe performed a case-control study including 674 IBD patients of the 1000IBD cohort, frequency-matched based on sex and age with 1348 controls from the population-based Lifelines Cohort Study. Exposome data were obtained using the validated Groningen IBD Environmental Questionnaire [GIEQ], capturing exposome factors through different stages of life using 844 items, of which 454 were applicable to study the role of 93 exposome factors in disease aetiology. Logistic regression [LR] modelling with Bonferroni correction for multiple testing was applied to estimate the multivariable-adjusted effect of each exposome factor.ResultsFor IBD, we identified four novel factors: stressful life events (CD odds ratio [OR] 2.61/UC OR 2.92), high perceived stress [2.29/2.67], alcohol use [0.40/0.43], and bronchial hyper-reactivity [3.04/2.36]. Four novel factors were associated with only CD: prenatal smoke exposure [1.89], having a bed partner [0.53], allergies [2.66], and cow’s milk hypersensitivity [5.87]; and two solely with UC: carpet flooring [0.57] and neuroticism [1.32]. Nine factors were replicated.ConclusionsIn this study we identified 10 novel, and replicated nine previously reported, exposome factors associated with IBD. Identifying these factors is important for both understanding disease aetiology and future prevention strategies to decrease the development of IBD in genetically susceptible persons.
Published: 2020

6. Long-Term Neurodevelopmental Outcomes in Children with Biliary Atresia

Author: Lyan H Rodijk, Henkjan J. Verkade, Behrooz Z. Alizadeh, Jan B F Hulscher, Ruben H J de Kleine, Janneke L. M. Bruggink, Anne E den Heijer, Clinical Neuropsychology, Center for Liver, Digestive and Metabolic Diseases (CLDM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Lifestyle Medicine (LM), Life Course Epidemiology (LCE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Male, Pediatrics, medicine.medical_specialty, Time Factors, Adolescent, medicine.medical_treatment, education, Population, INFANTS, Liver transplantation, DUTCH, Special education, Liver disease, Cognition, AGE, Biliary atresia, Biliary Atresia, QUALITY-OF-LIFE, medicine, Humans, Child, Motor skill, Netherlands, education.field_of_study, business.industry, Incidence, VERBAL-LEARNING TEST, medicine.disease, Prognosis, Liver Transplantation, Motor Skills, Neurodevelopmental Disorders, Pediatrics, Perinatology and Child Health, Female, business, Follow-Up Studies
Abstract: Objective: To assess long-term neurodevelopmental outcomes in school-aged children with biliary atresia. Study design: All Dutch children (6-12 years of age) diagnosed with biliary atresia were invited to participate in this study. We used validated neurodevelopmental tests to assess motor skills and cognition, and questionnaires to assess behavior. Scores were compared with the Dutch norm population, by means of 1-sample tests. Results are given as number and percentage or mean ± SD. Results: We included 46 children, with a median age of 11 years (range, 6-13 years); 36 children had undergone a liver transplantation (78%). Twelve children (26%) received special education (vs 2.4% in the norm population; P
Published: 2020

7. A two-stage genome-wide association study of radiation-induced acute toxicity in head and neck cancer

Author: Behrooz Z. Alizadeh, Hendrika Boezen, Roel J H M Steenbakkers, Johannes A. Langendijk, Johanna G M van den Hoek, Elnaz Naderi, Anne P G Crijns, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Damage and Repair in Cancer Development and Cancer Treatment (DARE)
Subjects: Oncology, medicine.medical_specialty, GENES, XRCC1, medicine.medical_treatment, Radiogenomics, Genome-wide association study, Single-nucleotide polymorphism, THERAPY, BREAST, Xerostomia, General Biochemistry, Genetics and Molecular Biology, Internal medicine, medicine, Mucositis, RADIOSENSITIVITY, Humans, GWAS, Prospective Studies, Saliva, Head and neck cancer, METAANALYSIS, business.industry, HERITABILITY, F-Box Proteins, Research, Area under the curve, General Medicine, Radiation-induced toxicity, medicine.disease, Radiation therapy, Head and Neck Neoplasms, ATM, Cohort, Medicine, business, RADIOTHERAPY, Genome-Wide Association Study
Abstract: Background Most head and neck cancer (HNC) patients receive radiotherapy (RT) and develop toxicities. This genome-wide association study (GWAS) was designed to identify single nucleotide polymorphisms (SNPs) associated with common acute radiation-induced toxicities (RITs) in an HNC cohort. Methods A two-stage GWAS was performed in 1279 HNC patients treated with RT and prospectively scored for mucositis, xerostomia, sticky saliva, and dysphagia. The area under the curve (AUC) was used to estimate the average load of toxicity during RT. At the discovery study, multivariate linear regression was used in 957 patients, and the top-ranking SNPs were tested in 322 independent replication cohort. Next, the discovery and the replication studies were meta-analyzed. Results A region on 5q21.3 containing 16 SNPs showed genome-wide (GW) significance association at P-value –8 with patient-rated acute xerostomia in the discovery study. The top signal was rs35542 with an adjusted effect size of 0.17*A (95% CI 0.12 to 0.23; P-value –9). The genome wide significant SNPs were located within three genes (EFNA5, FBXL17, and FER). In-silico functional analysis showed these genes may be involved in DNA damage response and co-expressed in minor salivary glands. We found 428 suggestive SNPs (P-value –5) for other toxicities, taken to the replication study. Eleven of them showed a nominal association (P-value Conclusions This GWAS suggested novel SNPs for patient-rated acute xerostomia in HNC patients. If validated, these SNPs and their related functional pathways could lead to a predictive assay to identify sensitive patients to radiation, which may eventually allow a more individualized RT treatment.
Published: 2021

8. Genetic insights into biological mechanisms governing human ovarian ageing

Author: Unnur Styrkarsdottir, Lynda M. Rose, Rehannah Borup, Anne B. Newman, Georgia Chenevix-Trench, Chikashi Terao, Jeremy A. Daniel, Christa Meisinger, Albert V. Smith, Emil Peter Thrane Hertz, Raymond Noordam, Wei He, Jennifer A. Smith, Mikael Eriksson, Konstantin Strauch, Daniel I. Chasman, Nicholas J. Timpson, Melissa A. Troester, Claudia Langenberg, Montserrat Garcia-Closas, Mohammad Arfan Ikram, Sara Lindström, Gad Rennert, Pascal Guénel, Kristina W. Olsen, Pierre Fontanillas, Ozren Polasek, Daniel F. Gudbjartsson, Frank B. Hu, Archie Campbell, Celine M. Vachon, Sheila Ulivi, Robin N Beaumont, Robert Karlsson, Lenore J. Launer, Renée de Mutsert, Annette Peters, David Schlessinger, Stefania Bandinelli, Rico Rueedi, Joop S.E. Laven, Pascal Timshel, Joanne M. Murabito, Kuang Lin, Jazib Hussain, Dennis O. Mook-Kanamori, Manjeet K. Bolla, Catherine E. Aiken, Javier Martin Gonzalez, Simon S. Cross, Immaculata De Vivo, Paul M. Ridker, Christopher A. Haiman, Gerardo Heiss, Jessica Tyrrell, Paul R. H. J. Timmers, Hironori Abe, Mike A. Nalls, Luigi Ferrucci, Natalia Perjakova, Jouke J. Hottenga, Robin G. Walters, Reedik Mägi, Niclas Håkansson, Miriam Dwek, Barbara McKnight, Sandra Turon, Stasa Stankovic, Linda Broer, Stephen J. Chanock, Martina La Bianca, Jenny Chang-Claude, Loic Le Marchand, Hamdi Mbarek, Doris Stöckl, Andrew F. Olshan, Graham G. Giles, James F. Wilson, Micaella Joaquim, Amruta Shrikhande, Eva Hoffmann, Stefania Benonisdottir, Ana Martínez-Marchal, Anthony J. Swerdlow, David Karasik, Nicholas J. Wareham, Peter A. Fasching, Jane L. Tarry-Adkins, Charles Kooperberg, Peter Vollenweider, Douglas F. Easton, Paula Aguilera, Jessica D. Faul, Patrik K. E. Magnusson, Emmanouil Saloustros, Alpa V. Patel, Ellen W. Demerath, Qin Wang, Aditya Sankar, Christopher G. Scott, Iffat Rahman, Sharon L.R. Kardia, Peter K. Joshi, Caterina Barbieri, Claus Yding Andersen, Tõnu Esko, Massimo Mezzavilla, Nicholas G. Martin, Rebecca D. Jackson, Alison D. Murray, Marina Ciullo, Nicholas Bowker, Anna Murray, Patrick Deelen, Zoltán Kutalik, Alicja Wolk, Manuela Gago-Dominguez, Eleonora Porcu, Laura Crisponi, Michela Traglia, Katharina E. Schraut, Antonietta Robino, Chunyan He, Bruce H. R. Wolffenbuttel, Henry Völzke, Daniela Ruggiero, John R. B. Perry, Lude Franke, Igor Rudan, Angela Cox, Unnur Þorsteinsdottir, Christian Gieger, David R. Weir, Jodie N. Painter, Martha S. Linet, Massimo Mangino, Melissa C. Southey, Petr Solc, Tim D. Spector, Christiana Kartsonaki, Momoko Horikoshi, Meir J. Stampfer, Eulalia Catamo, Mònica Ferrer-Roda, Ko Willems van Dijk, Daniela Toniolo, Caroline Hayward, Lili Milani, Chloé Sarnowski, Jian'an Luan, Behrooz Z. Alizadeh, Jenny A. Visser, Stig E. Bojesen, Genevieve Lachance, Ulrike Peters, Antonella Mulas, John J. Spinelli, Elnaz Naderi, Andrew R. Wood, Paul D.P. Pharoah, Elinor J. Sawyer, Annique Claringbould, Saleh Shekari, David G. Hunter, Marie Louise Grøndahl, Vilmundur Gudnason, Nora Franceschini, Dale P. Sandler, Dale R. Nyholt, Jacques E. Rossouw, Amber N. Wilcox, Thomas U. Ahearn, Hedy S. Rennert, Olivier B. Bakker, Jingmei Li, Francesco Cucca, Eric Boerwinkle, Matthias W. Beckmann, Cristina Menni, Minouk J. Schoemaker, Esther M. John, Tune H. Pers, Andrés J. López-Contreras, Tanguy Corre, Jonathan Marten, Alice M. Arnold, N. Charlotte Onland-Moret, Lucie Knoblochova, Anna Pujol, Kathryn L. Lunetta, Marjanka K. Schmidt, Teresa Nutile, Serena Sanna, Gonneke Willemsen, Roger L. Milne, Kristan J. Aronson, Frits R. Rosendaal, Murielle Bochud, Ken K. Ong, Susan M. Ring, Nancy L. Pedersen, Blair H. Smith, Ivana Kolcic, Annelie Augustinsson, Jose E. Castelao, Alexander Teumer, Felix R. Day, Sven Bergmann, Timothy M. Frayling, Lauren R. Teras, George Davey Smith, Thomas Meitinger, Alison M. Dunning, Ignasi Roig, Dorret I. Boomsma, Harald Grallert, Toshiko Tanaka, Katherine S. Ruth, Julie E. Buring, Marek Zygmunt, Uwe Völker, Irene L. Andrulis, Håkan Olsson, Harry Campbell, Cari M. Kitahara, Annika Lindblom, Yvonne T. van der Schouw, Cinzia Sala, Debbie A Lawlor, Joe Dennis, Yongmei Liu, Yan Huang, Stephen Burgess, Brumat Marco, Veronique Vitart, Kari Stefansson, Susan E. Ozanne, Kamila Czene, Simin Liu, John L. Hopper, Joyce B. J. van Meurs, Satoshi H. Namekawa, Miya Kudo Høffding, Fergus J. Couch, Ajuna Azad, Eco J. C. de Geus, Liming Li, Grant W. Montgomery, Peter Kraft, André G. Uitterlinden, Arto Mannermaa, Heiko Becher, Allison W. Kurian, Vallari Shukla, Zhengming Chen, Per Hall, Jennifer A. Brody, Rossella Sorice, Wei Zhao, Andres Metspalu, Sarah E. Medland, Tricia Lindstrom, Clarice R. Weinberg, Bruce M. Psaty, Thérèse Truong, Anna Marie Mulligan, Deborah J. Thompson, Patrick Sulem, Internal Medicine, Epidemiology, Obstetrics & Gynecology, Hoffmann, Eva R [0000-0002-2588-0652], Murray, Anna [0000-0002-2351-2522], Roig, Ignasi [0000-0003-0313-3581], Perry, John RB [0000-0001-6483-3771], Apollo - University of Cambridge Repository, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), Biological Psychology, APH - Mental Health, APH - Methodology, APH - Personalized Medicine, and APH - Health Behaviors & Chronic Diseases
Subjects: Gerontology, Aging, Far East, Endocrinology, Diabetes and Metabolism, Menopause, Premature, Genome-wide association study, VARIANTS, Primary Ovarian Insufficiency, Inbred C57BL, Bioinformatics, DISEASE, Healthy Aging, genetics of ovarian aging, Fragile X Mental Retardation Protein, Mice, Endocrinology, Medicine, EARLY MENOPAUSE, media_common, RISK, Multidisciplinary, Asia, Eastern, Reproduction, Longevity, Middle Aged, Europe, MENDELIAN RANDOMIZATION, Medical genetics, Female, ICEP, Menopause, Adult, Alleles, Animals, Bone and Bones, Checkpoint Kinase 1, Checkpoint Kinase 2, Diabetes Mellitus, Type 2, Diet, Fertility, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Mice, Inbred C57BL, Ovary, Uterus, Type 2, medicine.medical_specialty, media_common.quotation_subject, MEDLINE, Biology, Premature ovarian insufficiency, Article, genome-wide meta-analysis, SDG 3 - Good Health and Well-being, GERMLINE, Diabetes Mellitus, Genetic predisposition, Ovarian reserve, Premature, business.industry, Human genetics, CHROMOSOME SYNAPSIS, DNA-DAMAGE, Ageing, EXPRESSION ANALYSIS, business, MEIOTIC CELL-CYCLE
Abstract: Reproductive longevity is essential for fertility and influences healthy ageing in women1,2, but insights into its underlying biological mechanisms and treatments to preserve it are limited. Here we identify 290 genetic determinants of ovarian ageing, assessed using normal variation in age at natural menopause (ANM) in about 200,000 women of European ancestry. These common alleles were associated with clinical extremes of ANM; women in the top 1% of genetic susceptibility have an equivalent risk of premature ovarian insufficiency to those carrying monogenic FMR1 premutations3. The identified loci implicate a broad range of DNA damage response (DDR) processes and include loss-of-function variants in key DDR-associated genes. Integration with experimental models demonstrates that these DDR processes act across the life-course to shape the ovarian reserve and its rate of depletion. Furthermore, we demonstrate that experimental manipulation of DDR pathways highlighted by human genetics increases fertility and extends reproductive life in mice. Causal inference analyses using the identified genetic variants indicate that extending reproductive life in women improves bone health and reduces risk of type 2 diabetes, but increases the risk of hormone-sensitive cancers. These findings provide insight into the mechanisms that govern ovarian ageing, when they act, and how they might be targeted by therapeutic approaches to extend fertility and prevent disease. Hundreds of genetic loci associated with age at menopause, combined with experimental evidence in mice, highlight mechanisms of reproductive ageing across the lifespan.
Published: 2021

9. Folic acid intake and folate status and colorectal cancer risk

Author: Jabraeel Shaarbafi, Saeed Dastgiri, Sara Moazzen, Roya Dolatkhah, Geertruida H. de Bock, Jafar Sadegh Tabrizi, and Behrooz Z. Alizadeh
Subjects: Oncology, SERUM FOLATE, medicine.medical_specialty, Folic acid, Colorectal cancer, RED-CELL, Biological Availability, Nutritional Status, HOMOCYSTEINE, Cochrane Library, METABOLISM, Critical Care and Intensive Care Medicine, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, Internal medicine, DIETARY-INTAKE, COLON, ADENOMAS, medicine, Odds Ratio, Humans, 030212 general & internal medicine, Randomized Controlled Trials as Topic, FORTIFICATION, Nutrition and Dietetics, PLASMA FOLATE, business.industry, Case-control study, Odds ratio, medicine.disease, Folate status, Diet, B vitamins, Meta-analysis, 030220 oncology & carcinogenesis, Relative risk, Case-Control Studies, Dietary Supplements, Systematic review, B-VITAMINS, business, Colorectal Neoplasms, Cohort study
Abstract: Background & aims: To evaluate the controversies among the studies assessing the association between folic acid intake or folate status and colorectal cancer risk. Methods: PubMed, Cochrane library and references of related articles were searched from January 2000 to September 2016. Studies on folic acid intake or folate status and colorectal cancer or adenoma risk were included. Full text review was conducted for potentially eligible studies. Quality assessment was performed. Random-effects meta-analysis was used to estimate risk ratio and 95% Confidence Intervals. Analysis was conducted by Comprehensive Meta-Analysis software. Results: Folic acid supplement intake showed no significant effect on colorectal cancer risk in meta analysis of randomized controlled trials, RR: 1.07 (95% CI: 0.86-1.43). The effect on risk was not significant in cohort studies either; RR = 0.96 (95% CI: 0.76-1.21). However, there was significant reduced colorectal cancer risk in total folate intake in cohort studies; 0.71 (95% CI: 0.59-0.86). Odds Ratio was also significantly reduced in case control studies; 0.77 (95% CI: 0.62-0.95). Nevertheless once folate status was measured as Red Blood Cell folate content, no significant effect on colorectal cancer risk was observed; 1.05 (95% CI: 0.85-1.30). Conclusion: The differences in bioavailability and metabolism of synthetic folic acid and natural dietary folate as well as variation in the baseline characteristics of subjects and various methods of folate status assessment might be the main reasons for these controversies. Findings of present study highlight the importance of individualized folic acid supplement intake given the fact that the beneficiary effects of long term folic acid supplementation is not confirmed. (C) 2017 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.
Published: 2018

10. Prediction of Inflammatory Bowel Diseases using Genetic Risk Score in Asian populations

Author: Siew C. Ng, Michiaki Kubo, Atsushi Takahashi, Behrooz Z. Alizadeh, Jae Hee Cheon, Thelma B K, Keiko Yamazaki, Ajit Sood, Homayoon Vahedi, Suzanne van Sommeren, Reza Malekzadeh, Suk-Kyun Yang, Nasser Ebrahimi Daryani, Rinse K. Weersma, Sunny H. Wong, Rupa Banerjee, Won Ho Kim, and Shifteh Abedian
Subjects: medicine.medical_specialty, business.industry, Internal medicine, fungi, medicine, Inflammatory Bowel Diseases, Genetic risk, business, digestive system diseases
Abstract: Background and Aims: The incidence of Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and Ulcerative colitis (UC), is rising in Asian populations. We undertook a cross-population study to explore whether genetic risk scores (GRS) of IBD, CD and UC could explain their occurrence, and whether they can be used to predict disease occurrence in general populations from East Asia (EA) and Central Asia (CA). Methods We studied 9,698 subjects – 4,733 IBD patients (2,003 CD; 2,730 UC) and 4,965 matched controls – who had been genotyped using Immunochip. The subjects were from three East Asian (Japan, South Korea and China) and two Central Asian populations (India and Iran). We generated GRS for each population by combining information from up to 201 genome-wide significant IBD-associated variants to summarize the total load of genetic risk for each phenotype. We then estimated the explained variance and predictability of IBD using the GRS. Results IBD GRS could explain up to 4.40% and 4.14% of IBD variance at a significant level in East Asian and Central Asian populations, respectively, but, given a prevalence of 0.01% and 0.04% for IBD, these yield limited predictive probability. GRS for CD and UC separately proved less significant than GRS for IBD. Conclusion GRS alone can explain only a limited percentage of disease occurrence (
Published: 2021

11. An Observational Cohort of First Episode Psychosis in Iran: The Azeri Recent Onset Acute Phase Psychosis Survey (ARAS Cohort) Study Protocol

Author: Sara Farhang, Mehrdad Ghaemmaghami, Ali Reza Shafiee-Kandjani, Seyed Gholamreza Noorazar, Wim Veling, Ayyoub Malek, Mohammad Hossein Somi, Richard Bruggeman, Behrooz Z. Alizadeh, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: Psychiatry, cognition, Psychosis, medicine.medical_specialty, lcsh:RC435-571, business.industry, Social environment, Cognition, medicine.disease, schizophrenia, first episode psychosis (FEP), gene-environement interactions, Psychiatry and Mental health, Social support, Schizophrenia, lcsh:Psychiatry, social context, Cohort, Methods, medicine, Observational study, business, Cohort study
Abstract: Background: Most of our knowledge about the etiology, course, treatment, and outcome of schizophrenia spectrum and other psychotic disorders stems from Western countries. Data from populations living in other geographical areas and low- and middle-income countries, with different genomes (ethnicity) and exposomes (e.g., culture and social support, drugs of abuse, religion), will add to our knowledge of this complex disorder.Methods: The Azeri Acute phase/Recent onset psychosis Survey (ARAS) has been initiated to study the course of the disorder in patients with recent-onset psychosis using validated diagnostic tools and a comprehensive outcome monitoring system, aiming to reveal indicators for understanding the risk and resilience factors and for choosing the best-personalized treatment strategy. All participants will be evaluated for clinical signs and symptoms as well as risk and resilience factors and will be followed up for 1, 3, and 5 years for outcomes in several domains. A hierarchical cluster method will be applied to identify the number of clusters for each outcome. Defined models will be applied to assess the predictive value of cognition on symptomatic and functional outcomes at follow-up.Discussion: The ARAS cohort will yield significant academic- (research and education) and care-related achievements. ARAS data and experience will have value both in being a useful model for other parts of this region and in an expansion of the currently available knowledge.
Published: 2021

12. A Higher Incidence of Isolated Biliary Atresia in Rural Areas: Results from an Epidemiological Study in The Netherlands

Author: Henkjan J. Verkade, Daan B E van Wessel, Behrooz Z. Alizadeh, Jan B F Hulscher, Mark Nomden, Solomon Ioannou, Janneke L M Bruggink, Ruben H J de Kleine, Lifestyle Medicine (LM), Center for Liver, Digestive and Metabolic Diseases (CLDM), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Rural Population, Temporal clustering, medicine.medical_specialty, Veterinary medicine, medicine.disease_cause, Logistic regression, 03 medical and health sciences, 0302 clinical medicine, Biliary Atresia, Biliary atresia, 030225 pediatrics, Epidemiology, medicine, Humans, Netherlands, business.industry, Incidence, Incidence (epidemiology), Gastroenterology, Odds ratio, medicine.disease, Epidemiologic Studies, Pediatrics, Perinatology and Child Health, 030211 gastroenterology & hepatology, Rural area, Chlamydia trachomatis, business
Abstract: Objectives Environmental factors may be involved in the pathogenesis of biliary atresia (BA). This epidemiological study aimed to analyze the relationships between the incidence of BA, the incidence of confirmed viral or bacterial infections and population density, and geographical and temporal clustering of BA in the Netherlands. Study design Correlations between the monthly incidence of BA and the number of confirmed infections were assessed. BA incidence per province was calculated and compared to the province with highest population density. Birthplaces were classified as rural or urban. Temporal clustering of month of birth and month of conception were analyzed. We performed analyses for isolated BA (IBA) and syndromic BA (SBA) separately. Chi2, logistic regression, and Walter and Elwood test were used. Results A total of 262 IBA and 49 SBA patients, born between 1987 and 2018, were included. IBA incidence correlated to the number of confirmed infections of, for example, Chlamydia trachomatis (R = 0.14; P = 0.02) and adenovirus (R = 0.22; P = 0.005). We observed a higher incidence of IBA (0.75/10,000; odds ratio [OR] = 1.86; P = 0.04) and SBA (0.27/10,000; OR = 6.91; P = 0.001) in Groningen and a higher incidence of SBA in Gelderland (0.13/10,000; OR = 3.35; P = 0.03). IBA incidence was 68% higher in rural (0.67/10,000) versus urban areas (0.40/10,000) (P = 0.02). The estimated month of conception of patients with SBA clustered in November (85% increase compared to average SBA incidence [0.09/10,000; P = 0.04]). Conclusions IBA incidence correlated weakly with national confirmed infections. IBA and SBA incidence varied geographically in the Netherlands. IBA incidence was higher in rural than in urban areas, which may be explained decreased exposure to pathogens. Our results provide support for a role of environmental factors in the pathogenesis of IBA.
Published: 2021

13. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline

Author: Lukas Habegger, Charumathi Sabanayagam, Michael Preuss, Laura M. Raffield, Mary F. Feitosa, Bamidele O. Tayo, Kevin Ho, Leo-Pekka Lyytikäinen, Florian Kronenberg, Valencia Hui Xian Foo, Adrienne Tin, Michael Cantor, Nisha Bansal, Tarunveer S. Ahluwalia, Melanie Waldenberger, Sarah A. Pendergrass, Behrooz Z. Alizadeh, Wolfgang Koenig, Qiong Yang, Xiaodong Bai, Christoph Wanner, Ben Schöttker, Giovanni Coppola, A. R. Shuldiner, Leslie A. Lange, Piyush Gampawar, Markus Scholz, Tien Yin Wong, Mary L. Biggs, Morris Swertz, Alicia Hawes, Girish N. Nadkarni, Christina-Alexandra Schulz, Chiea Chuen Khor, Ricardo H. Ulloa, Jeffrey C. Staples, Miao-Li Chee, Laura M. Yerges-Armstrong, Andrew Blumenfeld, Karlhans Endlich, Bernhard Banas, Bruce H.R. Wolffenbuttel, Kai-Uwe Eckardt, Pavel Hamet, Carsten A. Böger, Harold Snieder, Marcus B. Jones, Judy Wang, Shih-Jen Hwang, Mathias Gorski, Anselm Hoppmann, Josyf C. Mychaleckyj, Bernd Holleczek, Pamela R. Matias-Garcia, Rainer Rettig, Karsten B. Sieber, Manasi Pradhan, Pashupati P. Mishra, Peter Rossing, Matthias Wuttke, Miao-Ling Chee, H. Marike Boezen, Yong Li, M. Arfan Ikram, Jeffrey G. Reid, Teresa Nutile, Maria Sotiropoulos Padilla, Lude Franke, Robert J. Carroll, Luca A. Lotta, Bernhard K. Krämer, Kjell Nikus, Jerome I. Rotter, Thomas Meitinger, Lars Wallentin, Cisca Wijmenga, Kent D. Taylor, Holly Kramer, Louis Widom, Olli T. Raitakari, Marcus E. Kleber, Man Li, Nina Hutri-Kähönen, Massimiliano Cocca, Reinhold Schmidt, John D. Overton, Cristian Pattaro, Michael Lattari, Sarah E. Wolf, Jin-Fang Chai, Karina Toledo, Brigitte Kühnel, Zhenhua Gu, Peter Almgren, Caitlin Forsythe, Yuri Milaneschi, Stephan J. L. Bakker, Layal Chaker, Dawn M. Waterworth, Silke Szymczak, James G. Wilson, Peter J. van der Most, Michelle L. O'Donoghue, William Salerno, Masayuki Yasuda, Sahar Ghasemi, Eric Boerwinkle, Josef Coresh, Ilja M. Nolte, Kia Manoochehri, Konstantin Strauch, Thomas D. Schleicher, Myriam Rheinberger, Audrey Y. Chu, Sanaz Sedaghat, Sandra Freitag-Wolf, Boting Ning, Matthias Nauck, Christina Beechert, Helena Schmidt, Harvey D. White, Nina Mononen, Johanne Tremblay, Navya Shilpa Josyula, Mika Kähönen, Katrin Horn, Andre Franke, Marianne Rots, Bettina Jung, Alexander R. Rosenkranz, Christian M. Shaffer, Mary Ann Lukas, Gerjan Navis, Christian Gieger, John Chalmers, Shareef Khalid, Uwe Völker, Marju Orho-Melander, Iris M. Heid, Brenda W.J.H. Penninx, A. Baras, Alexander Lopez, Evan Maxwell, Ruth J. F. Loos, Erin D. Fuller, Christa Meisinger, Gonçalo R. Abecasis, Suganthi Balasubramanian, Chris H. L. Thio, Martin H. de Borst, Stefan Coassin, Ching-Yu Cheng, Wolfgang Lieb, Kenneth Rice, Alexander Teumer, Mark Woodward, Gisu Eom, Hermann Brenner, Thomas W. Winkler, Anna Köttgen, Edith Hofer, Aris Economides, Ron T. Gansevoort, Pim van der Harst, Lyndon J. Mitnaul, Bruce M. Psaty, Erwin P. Bottinger, Olle Melander, Niek Verweij, Frauke Degenhardt, Yan Zhang, Mohsen Ghanbari, Veronika Wanner, Terho Lehtimäki, Leland Barnard, Tampere University, Primary Health Care, Department of Paediatrics, Clinical Medicine, Department of Clinical Physiology and Nuclear Medicine, Department of Clinical Chemistry, TAYS Heart Centre, Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Department of Marketing Management, Epidemiology, Internal Medicine, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, and APH - Digital Health
Subjects: 0301 basic medicine, medicine.medical_specialty, Genome-wide association study, 030232 urology & nephrology, Protein Disulfide-Isomerases, Hasso-Plattner-Institut für Digital Engineering GmbH, Renal function, Locus (genetics), Biology, AMP-Activated Protein Kinases, Kidney, 3121 Internal medicine, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, end-stage kidney disease, rapid eGFRcrea decline, Urologi och njurmedicin, medicine, Humans, Urology and Nephrology, ddc:610, Allele, Genetic association, Genetics, Creatinine, genome-wide association study, Acute kidney injury, acute kidney injury, medicine.disease, United Kingdom, ddc, 030104 developmental biology, chemistry, Nephrology, Medical genetics, 3111 Biomedicine, 610 Medizin und Gesundheit, Glomerular Filtration Rate
Abstract: Rapid decline of glomerular filtration rate estimated from creatinine (eGFRcrea) is associated with severe clinical endpoints. In contrast to cross-sectionally assessed eGFRcrea, the genetic basis for rapid eGFRcrea decline is largely unknown. To help define this, we meta-analyzed 42 genome-wide association studies from the Chronic Kidney Diseases Genetics Consortium and United Kingdom Biobank to identify genetic loci for rapid eGFRcrea decline. Two definitions of eGFRcrea decline were used: 3 mL/min/1.73m(2)/year or more ("Rapid3"; encompassing 34,874 cases, 107,090 controls) and eGFRcrea decline 25% or more and eGFRcrea under 60 mL/min/1.73m(2) at follow-up among those with eGFRcrea 60 mL/min/1.73m(2) or more at baseline ("CKDi25"; encompassing 19,901 cases, 175,244 controls). Seven independent variants were identified across six loci for Rapid3 and/or CKDi25: consisting of five variants at four loci with genome-wide significance (near UMOD-PDILT (2), PRKAG2, WDR72, OR2S2) and two variants among 265 known eGFRcrea variants (near GATM, LARP4B). All these loci were novel for Rapid3 and/or CKDi25 and our bioinformatic follow-up prioritized variants and genes underneath these loci. The OR2S2 locus is novel for any eGFRcrea trait including interesting candidates. For the five genome-wide significant lead variants, we found supporting effects for annual change in blood urea nitrogen or cystatin-based eGFR, but not for GATM or (LARP4B). Individuals at high compared to those at low genetic risk (8-14 vs. 0-5 adverse alleles) had a 1.20-fold increased risk of acute kidney injury (95% confidence interval 1.08-1.33). Thus, our identified loci for rapid kidney function decline may help prioritize therapeutic targets and identify mechanisms and individuals at risk for sustained deterioration of kidney function., Zweitveröffentlichungen der Universität Potsdam : Reihe der Digital Engineering Fakultät; 19
Published: 2021

14. Staple Food Fortification with Folic Acid and Iron and Gastrointestinal Cancers: Critical Appraisal of Long-Term National Fortification

Author: Saeed Dastgiri, Roya Dolatkhah, Geertruida H. de Bock, Behrooz Z. Alizadeh, Sara Moazzen, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and University of Groningen
Subjects: 0301 basic medicine, Cancer Research, medicine.medical_specialty, Gastrointestinal Neoplasms/epidemiology, Esophageal Neoplasms, Colorectal cancer, Iron, Fortification, Flour, Medicine (miscellaneous), Gastroenterology, COLORECTAL-CANCER, 03 medical and health sciences, 0302 clinical medicine, Folic Acid, CHILDBEARING AGE, Stomach Neoplasms, Internal medicine, medicine, Humans, Gastrointestinal cancer, Triticum, FLOUR FORTIFICATION, Gastrointestinal Neoplasms, Aged, RISK, 030109 nutrition & dietetics, Nutrition and Dietetics, ESOPHAGEAL, business.industry, Incidence (epidemiology), COLON-CANCER, Cancer, WOMEN, Staple food, Fortified, Middle Aged, medicine.disease, Confidence interval, Critical appraisal, Oncology, Food, FOLATE INTAKE, 030220 oncology & carcinogenesis, Food, Fortified, EAST AZERBAIJAN, business
Abstract: The co-occurrence of wheat flour fortification with folic acid and iron and gastrointestinal cancer incidences were critically assessed in the East Azerbaijan province in Northwest of Iran. In an ecological design, overall gastrointestinal cancer rate ratios and their 95% confidence intervals (95% CI) were calculated as primary outcome before (2004-2006) and after (2007-2015) the introduction of fortification. No consistent changes were observed in esophageal and gastric cancer, but the rate ratios of colorectal cancer increased significantly after fortification in the 35-54 years age group (women: 2.07, 95% CI: 1.79-2.49; men: 1.59, 95% CI: 1.33-1.89) and the 55-74 years age group (women 1.50, 95% CI: 1.27-1.76; men: 2.51, 95% CI: 2.13-2.95). The increased incidence of colorectal cancer was contemporary with long-term fortification; further investigation is required to establish the associations.
Published: 2021

15. Assessment of Diet Quality and Adherence to Dietary Guidelines in Gastrointestinal Cancer Survivors: A Cross-Sectional Study

Author: Barbara L. van Leeuwen, Francisco O Cortés-Ibañez, Behrooz Z. Alizadeh, Geertruida H. de Bock, Sara Moazzen, Clinical Cognitive Neuropsychiatry Research Program (CCNP), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Male, medicine.medical_specialty, Cross-sectional study, Population, esophageal neoplasms, lcsh:TX341-641, Diet Surveys, Article, Nutrition Policy, gastrointestinal neoplasms, 03 medical and health sciences, Eating, 0302 clinical medicine, Cancer Survivors, Internal medicine, medicine, Humans, 030212 general & internal medicine, Food components, Gastrointestinal cancer, education, Netherlands, education.field_of_study, Nutrition and Dietetics, stomach neoplasms, business.industry, Stomach, Cancer, social sciences, colorectal neoplasms, Middle Aged, medicine.disease, medicine.anatomical_structure, Cross-Sectional Studies, Diet quality, 030220 oncology & carcinogenesis, Case-Control Studies, Cohort, population characteristics, Female, Guideline Adherence, Diet, Healthy, business, diet, lcsh:Nutrition. Foods and food supply, human activities, Food Science
Abstract: Diet quality among short- and long-term gastrointestinal (GI) cancer survivors with different tumor sites was investigated compared to a reference population cohort. Diet quality of GI cancer survivors (n = 307) was compared to an age- and sex-matched reference population with no history of cancer (n = 3070). All were selected from Lifelines, a population-based cohort. GI cancers were defined as having a history of cancer of the bowel, esophagus, or stomach. Diet quality was assessed by a self-administrated food frequency questionnaire in terms of: (i) Lifelines Diet (LLD) scores, where higher scores indicate higher diet quality, (ii) the adherence to dietary guidelines, quantified by the percentage of meeting dietary recommendations, as given by Dutch dietary guidelines, and (iii) the mean daily intake of food components. All analyses were adjusted for lifestyle factors. Diet scores in GI cancer survivors were not different from the reference population (OR = 0.97, 95% CI: 0.73&ndash, 1.23). Stratification for time since diagnosis and tumor site gave similar results. The intake of vegetables, unsweetened dairies, and nuts and legumes was almost 50% lower than the recommended amount, and the mean intake of unhealthy food components was at least one serving/day among GI cancer survivors, as well as in the reference population. In the long run, GI cancer survivors do not differ from the reference population in their diet quality. In conclusion, both groups can improve their diet quality.
Published: 2020

16. Diet Quality and Upper Gastrointestinal Cancers Risk: A Meta-Analysis and Critical Assessment of Evidence Quality

Author: Kimberley W. J. van der Sloot, Behrooz Z. Alizadeh, Geertruida H. de Bock, Roel J. Vonk, and Sara Moazzen
Subjects: Adult, Male, medicine.medical_specialty, Mediterranean diet, ESOPHAGEAL CANCER, Pooling, SQUAMOUS-CELL CANCER, healthy diet, lcsh:TX341-641, Review, Diet, Mediterranean, esophageal neoplasm, gastrointestinal neoplasms, 03 medical and health sciences, 0302 clinical medicine, ADHERENCE, Risk Factors, Internal medicine, Medicine, Upper gastrointestinal, Humans, Grading (education), Aged, Aged, 80 and over, Inflammation, Nutrition and Dietetics, stomach neoplasms, business.industry, ADENOCARCINOMA, Odds ratio, Middle Aged, Confidence interval, Diet, MEDITERRANEAN DIET, Evidence quality, INFLAMMATORY INDEX, 030220 oncology & carcinogenesis, Meta-analysis, PATTERNS, 030211 gastroenterology & hepatology, Female, business, lcsh:Nutrition. Foods and food supply, GASTRIC-CANCER, Food Science
Abstract: We aimed to assess the effect of a high-quality diet on the risk of upper gastrointestinal cancer and to evaluate the overall quality of our findings by searching PubMed, EMBASE, Web of Science, Cochrane, and the references of related articles to February 2020. Two reviewers independently retrieved the data and performed the quality assessments. We defined the highest-quality diet as that with the lowest Diet Inflammatory Index category and the highest Mediterranean Diet Score category. Overall odds ratios and 95% confidence intervals were estimated for upper gastrointestinal cancer risk comparing the highest- versus lowest-diet quality. A random-effects meta-analysis was then applied with Review Manager, and the quality of the overall findings was evaluated with the Grading of Recommendations Assessment, Development, and Evaluation approach. The highest-quality diets were significantly associated with reduced risk of upper gastrointestinal cancers, achieving odds ratios of 0.59 (95% confidence interval: 0.48–0.72) for the Diet Inflammatory Index, pooling the findings from nine studies, and 0.72 (95% confidence interval: 0.61–0.88) for the Mediterranean Diet Score, pooling the findings from 11 studies. We observed a minimum of 69% heterogeneity in the pooled results. The pooled results were graded as low quality of evidence. Although it may be possible to offer evidence-based general dietary advice for the prevention of upper gastrointestinal cancers, the evidence is currently of insufficient quality to develop dietary recommendations.
Published: 2020

17. Folic Acid Supplement Intake and Risk of Colorectal Cancer in Women; A Case Control Study

Author: Saeed Dastgiri, Behrooz Z. Alizadeh, Geertruida H. de Bock, Hossein Mashhadi Abdolahi, Sara Moazzen, Roya Dolatkhah, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Basic and Translational Research and Imaging Methodology Development in Groningen (BRIDGE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Colorectal cancer, LOW FOLATE LEVELS, Information Storage and Retrieval, Infectious and parasitic diseases, RC109-216, Iran, 0302 clinical medicine, Risk Factors, Epidemiology, Odds Ratio, Neural Tube Defects, 030212 general & internal medicine, POPULATION, Original Research, education.field_of_study, FORTIFICATION, PLASMA FOLATE, 030503 health policy & services, Confounding, General Medicine, Middle Aged, Vitamin B Complex, Female, Public aspects of medicine, RA1-1270, Colorectal Neoplasms, 0305 other medical science, Adult, medicine.medical_specialty, Population, 03 medical and health sciences, Folic Acid, AGE, Internal medicine, COLON, medicine, Humans, education, Aged, Duration of Therapy, business.industry, Case-control study, Odds ratio, Protective Factors, medicine.disease, Confidence interval, Cancer registry, Logistic Models, Case-Control Studies, business
Abstract: Background: An ongoing controversy exists on the role of folic acid supplementation in colorectal cancer risk among epidemiological studies.Objective: To assess the association between maternal folic acid supplementation and colorectal cancer risk.Methods: A paired matched case control study of 405 subjects was performed, including women residing in 135 villages of East Azerbaijan, Iran. Per area, subjects were followed regularly in local healthcare centers, where health- and social-related information have been collected prospectively in face to face interviews by well-trained health workers. We extracted folic acid supplement intake, baseline characteristics, and confounders from healthcare records. The data for study participants were linked to national cancer registry repositories, from which we retrieved the data of 135 women diagnosed with colorectal cancer between 2005 to 2015. Two hundred seventy controls were individually matched with cases in terms of residing village, age, and gender. We applied multivariate conditional logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs).Findings: There was no significant association between folic acid supplementation and colorectal cancer risk in those with history of folic acid intake compared to those with no history of intake (OR 0.95; 95% CI 0.59 to 1.53), in those with less than five years of folic acid (0.79; 0.45 to 1.39) or in those with ≥5 years intake (1.09; 0.52 to 2.26). This risk did not change after adjustment for covariates or further stratification.Conclusions: Maternal folic acid supplementation did not affect colorectal cancer risk in a population where supplemental folic acid is prescribed with regular intervals for women of child-bearing age.
Published: 2020

18. Habitual dietary intake of IBD patients differs from population controls: a case-control study

Author: Behrooz Z. Alizadeh, Ettje F Tigchelaar-Feenstra, Lude Franke, Marjo J E Campmans-Kuijpers, Jackie A M Dekens, Vera Peters, Gerard Dijkstra, Morris A. Swertz, Cisca Wijmenga, Rinse K. Weersma, Floris Imhann, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Institute for Organ Transplantation (GIOT)
Subjects: medicine.medical_specialty, Population, Medicine (miscellaneous), ENVIRONMENTAL-FACTORS, Disease course, Food group, 03 medical and health sciences, Eating, 0302 clinical medicine, Environmental health, Epidemiology, EPIDEMIOLOGY, Medicine, Humans, 030212 general & internal medicine, Sugar, education, education.field_of_study, Nutrition and Dietetics, business.industry, Dietary intake, digestive, oral, and skin physiology, Case-control study, food and beverages, CONSUMPTION, Feeding Behavior, Original Contribution, medicine.disease, Inflammatory Bowel Diseases, CROHNS-DISEASE, Diet, Malnutrition, Multinomial logistic regression analysis, ULCERATIVE-COLITIS, Case-Control Studies, Dietary assessment, Inflammatory bowel disease (IBD), RISK-FACTORS, LIFE-STYLE, NUTRITION, 030211 gastroenterology & hepatology, FATTY-ACIDS, business, Food frequency questionnaire (FFQ), INFLAMMATORY-BOWEL-DISEASE
Abstract: Background Since evidence-based dietary guidelines are lacking for IBD patients, they tend to follow “unguided” dietary habits; potentially leading to nutritional deficiencies and detrimental effects on disease course. Therefore, we compared dietary intake of IBD patients with controls. Methods Dietary intake of macronutrients and 25 food groups of 493 patients (207 UC, 286 CD), and 1291 controls was obtained via a food frequency questionnaire. Results 38.6% of patients in remission had protein intakes below the recommended 0.8 g/kg and 86.7% with active disease below the recommended 1.2 g/kg. Multinomial logistic regression, corrected for age, gender and BMI, showed that (compared to controls) UC patients consumed more meat and spreads, but less alcohol, breads, coffee and dairy; CD patients consumed more non-alcoholic drinks, potatoes, savoury snacks and sugar and sweets but less alcohol, dairy, nuts, pasta and prepared meals. Patients with active disease consumed more meat, soup and sugar and sweets but less alcohol, coffee, dairy, prepared meals and rice; patients in remission consumed more potatoes and spreads but less alcohol, breads, dairy, nuts, pasta and prepared meals. Conclusions Patients avoiding potentially favourable foods and gourmandizing potentially unfavourable foods are of concern. Special attention is needed for protein intake in the treatment of these patients.
Published: 2019

19. Blood Eosinophil Count and Metabolic, Cardiac and Pulmonary Outcomes: A Mendelian Randomization Study

Author: Behrooz Z. Alizadeh, Judith M. Vonk, Harold Snieder, Bruce H. R. Wolffenbuttel, Gerard H. Koppelman, Lude Franke, Marcel Bruinenberg, Gerjan Navis, H. Marike Boezen, Daniel I. Chasman, Marzyeh Amini, Ali Abbasi, Bram P. Prins, Pim van der Harst, Abbasi, Ali [0000-0002-6452-4765], Prins, Bram [0000-0001-5774-034X], Koppelman, Gerard H [0000-0001-8567-3252], Apollo - University of Cambridge Repository, Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), Value, Affordability and Sustainability (VALUE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Blood Glucose, Male, 0301 basic medicine, LOCI, Blood Pressure, Genome-wide association study, metabolic diseases, Body Mass Index, Cohort Studies, Leukocyte Count, Pulmonary Disease, Chronic Obstructive, 0302 clinical medicine, Forced Expiratory Volume, Glucose homeostasis, 030212 general & internal medicine, Genetics (clinical), Metabolic Syndrome, Obstetrics and Gynecology, Mendelian Randomization Analysis, Lipids, medicine.anatomical_structure, Cohort, CORONARY-ARTERY-DISEASE, Female, medicine.medical_specialty, eosinophil count, PROVIDES INSIGHTS, CONTROLLED-TRIAL, genetic risk score, GENETIC ARCHITECTURE, 03 medical and health sciences, Quantitative Trait, Heritable, Internal medicine, Mendelian randomization, medicine, Humans, complex diseases, CELL, GENOME-WIDE ASSOCIATION, METAANALYSIS, Glycated Hemoglobin, business.industry, Odds ratio, Eosinophil, medicine.disease, Asthma, instrumental variable, cardiovascular diseases, 030104 developmental biology, Diabetes Mellitus, Type 2, Pediatrics, Perinatology and Child Health, GLUCOSE-HOMEOSTASIS, pulmonary diseases, TYPE-2 DIABETES RISK, Metabolic syndrome, business, Genome-Wide Association Study
Abstract: Blood eosinophil count is associated with a variety of common complex outcomes in epidemiological observation. The aim of this study was to explore the causal association between determined blood eosinophil count and 20 common complex outcomes (10 metabolic, 6 cardiac, and 4 pulmonary). Through Mendelian randomization, we investigated genetic evidence for the genetically determined eosinophil in association with each outcomes using individual-level LifeLines cohort data (n = 13,301), where a weighted eosinophil genetic risk score comprising five eosinophil associated variants was created. We further examined the associations of the genetically determined eosinophil with those outcomes using summary statistics obtained from genome-wide association study consortia (6 consortia and 14 outcomes). Blood eosinophil count, by a 1-SD genetically increased, was not statistically associated with common complex outcomes in the LifeLines. Using the summary statistics, we showed that a higher genetically determined eosinophil count had a significant association with lower odds of obesity (odds ratio (OR) 0.81, 95% confidence interval (CI) [0.74, 0.89]) but not with the other traits and diseases. To conclude, an elevated eosinophil count is unlikely to be causally associated to higher risk of metabolic, cardiac, and pulmonary outcomes. Further studies with a stronger genetic risk score for eosinophil count may support these results.
Published: 2018

20. A transnational collaborative network dedicated to the study and applications of the vascular endothelial growth factor-A in medical practice: the VEGF Consortium

Author: George Dedoussis, Jochen G. Schneider, Sudha Seshadri, Mary Jo Kurth, Alex Ander Aldasoro Arguinano, Daniela Ruggiero, Georges Dagher, Marina Ciullo, Ting Xie, Vesna Gorenjak, Panagiotis Deloukas, Sophie Visvikis-Siest, Federico Innocenti, Jérôme Chatelin, George Weryha, Janja Marc, Behrooz Z. Alizadeh, John Victor Lamont, Marc Rancier, Maria G. Stathopoulou, Alexandros M. Petrelis, Jean-Louis Merlin, Maurizio Simmaco, Ron H.N. van Schaik, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), Dietetics and Nutrition, Harokopio University of Athens, Department of Nutrition-Dietetics, Randox Laboratories, 2nd Faculty of Medicine, Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Institut de Cancérologie de Lorraine - Alexis Vautrin [Nancy] (UNICANCER/ICL), UNICANCER, Centre de Recherche en Automatique de Nancy (CRAN), Université de Lorraine (UL)-Centre National de la Recherche Scientifique (CNRS), Institute of Genetics and Biophysics, CNR, Naples, Neurology Department, Boston University School of Medicine (BUSM), Boston University [Boston] (BU)-Boston University [Boston] (BU), Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL)
Subjects: Vascular Endothelial Growth Factor A, 0301 basic medicine, Oncology, medicine.medical_specialty, Biomedical Research, Systems Analysis, International Cooperation, [SDV]Life Sciences [q-bio], Collaborative network, Clinical Biochemistry, Population, MEDLINE, [SDV.CAN]Life Sciences [q-bio]/Cancer, Bioinformatics, VEGF-A, AUTOIMMUNE THYROID-DISEASES, 03 medical and health sciences, DESIGN, collaborative network, multidisciplinary genomic studies, personalized medicine, Internal medicine, Humans, Medicine, COHORT, Precision Medicine, education, ComputingMilieux_MISCELLANEOUS, POPULATION, education.field_of_study, PLASMA, business.industry, Biochemistry (medical), Medical practice, General Medicine, Precision medicine, 3. Good health, Vascular endothelial growth factor A, 030104 developmental biology, Cohort, Personalized medicine, BONE, business
Abstract: International audience
Published: 2017

21. Familial liability to psychosis is a risk factor for multimorbidity in people with psychotic disorders and their unaffected siblings

Author: P.J. Quee, Frederike Schirmbeck, Behrooz Z. Alizadeh, Philippe Delespaul, René S. Kahn, E. R. van den Heuvel, R. van Winkel, Agna A. Bartels-Velthuis, Harold Snieder, M.F.H. Khan, N. J. M. van Beveren, Wiepke Cahn, J. van Os, N.E.M. van Haren, Carin J. Meijer, Inez Myin-Germeys, Claudia J. P. Simons, Richard Bruggeman, L. de Haan, Md. Atiqul Islam, Neurosciences, Psychiatry, Stochastic Operations Research, Statistics, APH - Mental Health, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, RS: MHeNs - R2 - Mental Health, Psychiatrie & Neuropsychologie, Promovendi MHN, PharmacoTherapy, -Epidemiology and -Economics, Life Course Epidemiology (LCE), Perceptual and Cognitive Neuroscience (PCN), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Clinical Cognitive Neuropsychiatry Research Program (CCNP), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Adult, Male, Psychosis, Pediatrics, medicine.medical_specialty, Physical health, Disease, CO-MORBIDITY, SDG 3 – Goede gezondheid en welzijn, Young Adult, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, Risk Factors, GENERAL-PRACTICE, Journal Article, Prevalence, medicine, Humans, 030212 general & internal medicine, Bipolar disorder, Young adult, Risk factor, Familial liability, Psychiatry, MAJOR DEPRESSIVE DISORDER, PHYSICAL ILLNESS, Siblings, SEVERE MENTAL-ILLNESS, Case-control study, Multimorbidity, BIPOLAR DISORDER, Middle Aged, medicine.disease, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, Case-Control Studies, HEALTH-CARE, CHRONIC DISEASE, Major depressive disorder, Female, Psychology, 030217 neurology & neurosurgery, Personality
Abstract: Background:Multimorbidity may impose an overwhelming burden on patients with psychosis and is affected by gender and age. Our aim is to study the independent role of familial liability to psychosis as a risk factor for multimorbidity.Methods:We performed the study within the framework of the Genetic Risk and Outcome of Psychosis (GROUP) project. Overall, we compared 1024 psychotic patients, 994 unaffected siblings and 566 controls on the prevalence of 125 lifetime diseases, and 19 self-reported somatic complaints. Multimorbidity was defined as the presence of two or more complaints/diseases in the same individual. Generalized linear mixed model (GLMM) were used to investigate the effects of gender, age (adolescent, young, older) and familial liability (patients, siblings, controls) and their interactions on multimorbidity.Results:Familial liability had a significant effect on multimorbidity of either complaints or diseases. Patients had a higher prevalence of multimorbidity of complaints compared to siblings (OR 2.20, 95% CI 1.79–2.69, P < 0.001) and to controls (3.05, 2.35–3.96, P < 0.001). In physical health multimorbidity, patients (OR 1.36, 95% CI 1.05–1.75, P = 0.018), but not siblings, had significantly higher prevalence than controls. Similar finding were observed for multimorbidity of lifetime diseases, including psychiatric diseases. Significant results were observed for complaints and disease multimorbidity across gender and age groups.Conclusion:Multimorbidity is a common burden, significantly more prevalent in patients and their unaffected siblings. Familial liability to psychosis showed an independent effect on multimorbidity; gender and age are also important factors determining multimorbidity.
Published: 2017

22. Visceral Adiposity, Genetic Susceptibility, and Risk of Complications Among Individuals with Crohnʼs Disease

Author: Paul Lochhead, Behrooz Z. Alizadeh, Katherine K. Gilpin, Kimberley W. J. van der Sloot, Ashwin N. Ananthakrishnan, Amit Joshi, John J. Garber, Ramnik J. Xavier, Kathleen O. Stewart, Vijay Yajnik, Hamed Khalili, Cosmas Giallourakis, Danielle Bellavance, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Male, obesity, Pathology, GUT MICROBIOME, Inflammatory bowel disease, Gastroenterology, 0302 clinical medicine, Crohn Disease, Odds Ratio, Immunology and Allergy, Medicine, Prospective Studies, Registries, visceral adipose tissue, Prospective cohort study, POPULATION, Adiposity, education.field_of_study, Crohn's disease, ASSOCIATION, FAT AREA, Massachusetts, ULCERATIVE-COLITIS, 030220 oncology & carcinogenesis, Disease Progression, Female, 030211 gastroenterology & hepatology, Adult, medicine.medical_specialty, Adolescent, Population, Intra-Abdominal Fat, Article, Young Adult, 03 medical and health sciences, Internal medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, education, Adiponectin, business.industry, Odds ratio, medicine.disease, BODY-MASS INDEX, Logistic Models, TISSUE, Tomography, X-Ray Computed, FOLLOW-UP, business, Crohn's disease complications, genetic predisposition, Body mass index, INFLAMMATORY-BOWEL-DISEASE
Abstract: Introduction: Adipose tissue in mesenteric fat plays a key role in systemic and luminal inflammation through production of Tumor Necrosis Factor-α (TNF-α) and inhibition of adiponectin, an anti-inflammatory cytokine, in patients with Crohn's disease (CD). However, little is known about the role of visceral adipose tissue (VAT) and its interaction with genetic predisposition on CD progression. We therefore sought to examine the association between VAT and its interaction with genetic susceptibility on risk of CD complications. Methods: We conducted a cross-sectional study of CD patients enrolled in Prospective Registry in Inflammatory Bowel Disease Study at Massachusetts General Hospital (PRISM). Information on diagnosis of CD and its complications were collected and confirmed through review of medical records. VAT volume was measured from CT scans prior to development of disease complications, using Aquarius 3D (TeraRecon Inc., version 4.4.12). A genetic risk score was calculated using previously reported single nucleotide polymorphisms (SNPs) associated genome-wide with CD susceptibility. We used logistic regression models to estimate the multivariable-adjusted odds ratio (MV-adjusted OR) and 95% confidence interval (CI) while adjusting for age at diagnosis, duration of disease, body mass index (BMI), and smoking. We evaluated for effect modification by genetic predisposition using multiplicative interaction terms. Results: Among 470 CD patients with available data on VAT, 73 required surgery, 57 with penetrating disease, 60 with stricturing disease, and 143 with perianal disease. The risk of surgery appeared to increase with higher VAT volume (Ptrend = 0.007). Specifically, compared to individuals in the lowest quartile of VAT volume (≤ 904 cm3), the MV-adjusted OR of surgery among individuals in the highest quartile (> 3809 cm3) was 5.75 (95% CI, 1.61-20.56). We did not observe an association between VAT volume and risk of penetrating, structuring, or perianal disease (All Ptrend > 0.40). We also explored the possibility that the effect of VAT on CD complications may be modified by genetic predisposition as assessed by genetic risk score and observed no effect modification (All Pinteraction > 0.25). Conclusions: In this cohort of patients with CD, we show that VAT volume measured prior to development of disease complications may be associated with a significantly increase in risk of surgery. Taken together with previous findings that BMI is not associated with risk of CD complications, our data suggest that visceral adiposity as measured by VAT and not total obesity, may negatively impact long-term progression of CD. (Figure Presented).
Published: 2017

23. T152. AZERI RECENT ONSET ACUTE PHASE PSYCHOSIS SURVEY (ARAS COHORT): PRELIMINARY REPORTS FROM AN OBSERVATIONAL COHORT OF FIRST EPISODE PSYCHOSIS IN IRAN

Author: Gholamreza Noorazar, Sara Farhang, Ayyoub Malek, Behrooz Z. Alizadeh, Ali Reza Shafiee-Kandjani, Mehrdad Ghaemmaghami, Wim Veling, and Richard Bruggeman
Subjects: Poster Session III, Psychosis, Pediatrics, medicine.medical_specialty, AcademicSubjects/MED00810, business.industry, medicine.disease, Psychiatry and Mental health, First episode psychosis, Cohort, medicine, Observational study, Recent onset, business
Abstract: Background Azeri Acute phase/Recent onset psychosis Survey (ARAS) is the first from central Asia to study the course of patients with recent onset psychosis. The aim is to reveal indicators for understanding the risk and resilience factors, and for choosing the best personalized treatment strategy. Methods The catchment area is north-west of Iran, with the majority having an Azeri ethnic background. All participants are evaluated for clinical signs and symptoms as well as risk and resilient factors and followed up for outcome in several domains. Here we give report of first 100 registered patients (male/female: 1.6). Results Patients are diagnosed with schizophrenia (23), brief psychotic disorder (4), schizophrenifom (9), amphetamine induced psychotic disorder (12), psychotic disorder NOS and schizoaffective (27). The mean score of PANSS was 26.79±20.62. Their mean age is 29.8±11.5. High school diploma or higher was achieved by 45. While 60 were single, 21 were married at the moment and 35 had children. All of patients were Muslims, 30 scored moderate on religiosity and the remaining scored high. Level of multidimensional perceived social support was moderate and high in 80 patients. Only 4 were living alone. Level of internalized stigma was moderate and high in 16 patients. Metabolic syndrome was diagnosed in 11. Almost one third of patients had ever used substance including cigarette (20), alcohol (12), opioids (5), amphetamine (15) and cannabis (5). The most prevalent prescribed medication is risperidone (78). Metabolic syndrome criteria were fulfilled in 16 patients. Discussion Preliminary reports from ARAS cohort shows few differences between Iranian and European patients. Lower rate of metabolic syndrome, substance use (especially cannabis) and higher rate of religiosity, having social support, married situation and having children are noticed.
Published: 2020

24. Genome Analyses of >200,000 Individuals Identify 58 Loci for Chronic Inflammation and Highlight Pathways that Link Inflammation and Complex Disorders

Author: Symen Ligthart, Ahmad Vaez, Urmo Võsa, Maria G. Stathopoulou, Paul S. de Vries, Bram P. Prins, Peter J. Van der Most, Toshiko Tanaka, Elnaz Naderi, Lynda M. Rose, Ying Wu, Robert Karlsson, Maja Barbalic, Honghuang Lin, René Pool, Gu Zhu, Aurélien Macé, Carlo Sidore, Stella Trompet, Massimo Mangino, Maria Sabater-Lleal, John P. Kemp, Ali Abbasi, Tim Kacprowski, Niek Verweij, Albert V. Smith, Tao Huang, Carola Marzi, Mary F. Feitosa, Kurt K. Lohman, Marcus E. Kleber, Yuri Milaneschi, Christian Mueller, Mahmudul Huq, Efthymia Vlachopoulou, Leo-Pekka Lyytikäinen, Christopher Oldmeadow, Joris Deelen, Markus Perola, Jing Hua Zhao, Bjarke Feenstra, Marzyeh Amini, Jari Lahti, Katharina E. Schraut, Myriam Fornage, Bhoom Suktitipat, Wei-Min Chen, Xiaohui Li, Teresa Nutile, Giovanni Malerba, Jian’an Luan, Tom Bak, Nicholas Schork, Fabiola Del Greco M., Elisabeth Thiering, Anubha Mahajan, Riccardo E. Marioni, Evelin Mihailov, Joel Eriksson, Ayse Bilge Ozel, Weihua Zhang, Maria Nethander, Yu-Ching Cheng, Stella Aslibekyan, Wei Ang, Ilaria Gandin, Loïc Yengo, Laura Portas, Charles Kooperberg, Edith Hofer, Kumar B. Rajan, Claudia Schurmann, Wouter den Hollander, Tarunveer S. Ahluwalia, Jing Zhao, Harmen H.M. Draisma, Ian Ford, Nicholas Timpson, Alexander Teumer, Hongyan Huang, Simone Wahl, YongMei Liu, Jie Huang, Hae-Won Uh, Frank Geller, Peter K. Joshi, Lisa R. Yanek, Elisabetta Trabetti, Benjamin Lehne, Diego Vozzi, Marie Verbanck, Ginevra Biino, Yasaman Saba, Ingrid Meulenbelt, Jeff R. O’Connell, Markku Laakso, Franco Giulianini, Patrik K.E. Magnusson, Christie M. Ballantyne, Jouke Jan Hottenga, Grant W. Montgomery, Fernando Rivadineira, Rico Rueedi, Maristella Steri, Karl-Heinz Herzig, David J. Stott, Cristina Menni, Mattias Frånberg, Beate St. Pourcain, Stephan B. Felix, Tune H. Pers, Stephan J.L. Bakker, Peter Kraft, Annette Peters, Dhananjay Vaidya, Graciela Delgado, Johannes H. Smit, Vera Großmann, Juha Sinisalo, Ilkka Seppälä, Stephen R. Williams, Elizabeth G. Holliday, Matthijs Moed, Claudia Langenberg, Katri Räikkönen, Jingzhong Ding, Harry Campbell, Michele M. Sale, Yii-Der I. Chen, Alan L. James, Daniela Ruggiero, Nicole Soranzo, Catharina A. Hartman, Erin N. Smith, Gerald S. Berenson, Christian Fuchsberger, Dena Hernandez, Carla M.T. Tiesler, Vilmantas Giedraitis, David Liewald, Krista Fischer, Dan Mellström, Anders Larsson, Yunmei Wang, William R. Scott, Matthias Lorentzon, John Beilby, Kathleen A. Ryan, Craig E. Pennell, Dragana Vuckovic, Beverly Balkau, Maria Pina Concas, Reinhold Schmidt, Carlos F. Mendes de Leon, Erwin P. Bottinger, Margreet Kloppenburg, Lavinia Paternoster, Michael Boehnke, A.W. Musk, Gonneke Willemsen, David M. Evans, Pamela A.F. Madden, Mika Kähönen, Zoltán Kutalik, Magdalena Zoledziewska, Ville Karhunen, Stephen B. Kritchevsky, Naveed Sattar, Genevieve Lachance, Robert Clarke, Tamara B. Harris, Olli T. Raitakari, John R. Attia, Diana van Heemst, Eero Kajantie, Rossella Sorice, Giovanni Gambaro, Robert A. Scott, Andrew A. Hicks, Luigi Ferrucci, Marie Standl, Cecilia M. Lindgren, John M. Starr, Magnus Karlsson, Lars Lind, Jun Z. Li, John C. Chambers, Trevor A. Mori, Eco J.C.N. de Geus, Andrew C. Heath, Nicholas G. Martin, Juha Auvinen, Brendan M. Buckley, Anton J.M. de Craen, Melanie Waldenberger, Konstantin Strauch, Thomas Meitinger, Rodney J. Scott, Mark McEvoy, Marian Beekman, Cristina Bombieri, Paul M. Ridker, Karen L. Mohlke, Nancy L. Pedersen, Alanna C. Morrison, Dorret I. Boomsma, John B. Whitfield, David P. Strachan, Albert Hofman, Peter Vollenweider, Francesco Cucca, Marjo-Riitta Jarvelin, J. Wouter Jukema, Tim D. Spector, Anders Hamsten, Tanja Zeller, André G. Uitterlinden, Matthias Nauck, Vilmundur Gudnason, Lu Qi, Harald Grallert, Ingrid B. Borecki, Jerome I. Rotter, Winfried März, Philipp S. Wild, Marja-Liisa Lokki, Michael Boyle, Veikko Salomaa, Mads Melbye, Johan G. Eriksson, James F. Wilson, Brenda W.J.H. Penninx, Diane M. Becker, Bradford B. Worrall, Greg Gibson, Ronald M. Krauss, Marina Ciullo, Gianluigi Zaza, Nicholas J. Wareham, Albertine J. Oldehinkel, Lyle J. Palmer, Sarah S. Murray, Peter P. Pramstaller, Stefania Bandinelli, Joachim Heinrich, Erik Ingelsson, Ian J. Deary, Reedik Mägi, Liesbeth Vandenput, Pim van der Harst, Karl C. Desch, Jaspal S. Kooner, Claes Ohlsson, Caroline Hayward, Terho Lehtimäki, Alan R. Shuldiner, Donna K. Arnett, Lawrence J. Beilin, Antonietta Robino, Philippe Froguel, Mario Pirastu, Tine Jess, Wolfgang Koenig, Ruth J.F. Loos, Denis A. Evans, Helena Schmidt, George Davey Smith, P. Eline Slagboom, Gudny Eiriksdottir, Andrew P. Morris, Bruce M. Psaty, Russell P. Tracy, Ilja M. Nolte, Eric Boerwinkle, Sophie Visvikis-Siest, Alex P. Reiner, Myron Gross, Joshua C. Bis, Lude Franke, Oscar H. Franco, Emelia J. Benjamin, Daniel I. Chasman, Josée Dupuis, Harold Snieder, Abbas Dehghan, Behrooz Z. Alizadeh, H. Marike Boezen, Gerjan Navis, Marianne Rots, Morris Swertz, Bruce H.R. Wolffenbuttel, Cisca Wijmenga, Emelia Benjamin, Tarunveer Singh Ahluwalia, James Meigs, Russell Tracy, Josh Bis, Nathan Pankratz, Alex Rainer, James G. Wilson, Josee Dupuis, Bram Prins, Urmo Vaso, Maria Stathopoulou, Terho Lehtimaki, Yalda Jamshidi, Sophie Siest, Andre G. Uitterlinden, Mohammadreza Abdollahi, Renate Schnabel, Ursula M. Schick, Aldi Kraja, Yi-Hsiang Hsu, Daniel S. Tylee, Alyson Zwicker, Rudolf Uher, George Davey-Smith, Andrew Hicks, Cornelia M. van Duijn, Cavin Ward-Caviness, J. Rotter, Ken Rice, Leslie Lange, Eco de Geus, Kari Matti Makela, David Stacey, Johan Eriksson, Tim M. Frayling, Eline P. Slagboom, Erasmus University Medical Center [Rotterdam] (Erasmus MC), University Medical Center Groningen [Groningen] (UMCG), University of Isfahan, University of Tartu, Interactions Gène-Environnement en Physiopathologie Cardio-Vasculaire (IGE-PCV), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lorraine (UL), The University of Texas Health Science Center at Houston (UTHealth), National Institute on Aging [Bethesda, USA] (NIA), National Institutes of Health [Bethesda] (NIH), Brigham and Women's Hospital [Boston], University of North Carolina [Chapel Hill] (UNC), University of North Carolina System (UNC), Department of Medical Epidemiology and Biostatistics (MEB), Karolinska Institutet [Stockholm], University of Split, Boston University School of Medicine (BUSM), Boston University [Boston] (BU), Process & Energy Laboratory, Delft University of Technology (TU Delft), Grand Lyon : communauté urbaine de Lyon, Interuniversity Cardiology Institute Netherlands, Department of Twin Research and Genetic Epidemiology, King's College London, London, Huazhong University of Science and Technology [Wuhan] (HUST), Division of Statistical Genomics, Washington University School of Medicine, Department of Psychiatry, VU University Medical Center [Amsterdam], Institut fuer Theoretische Physik (Institut fuer Theoretische Physik), Universität Heidelberg [Heidelberg] = Heidelberg University, Molecular Epidemiology, MRC Epidemiology Unit, Institute of Metabolic Science, Addenbrooke's Hospital, Mahidol University [Bangkok], Northwest A and F University, Laboratoire d'Optimisation des Systèmes Industriels (LOSI), Institut Charles Delaunay (ICD), Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS)-Université de Technologie de Troyes (UTT)-Centre National de la Recherche Scientifique (CNRS), Institute of Genetics and Biophysics, CNR, Naples, Università degli studi di Verona = University of Verona (UNIVR), Department of Molecular Medicine [Scripps Research Institute], The Scripps Research Institute [La Jolla, San Diego], Department of Physics, Indian Institute of Technology Kanpur (IIT Kanpur), Deptartment of Medical Biochemistry and Microbiology, Uppsala University, Department of Electrical and Computer Engineering [Waterloo] (ECE), University of Waterloo [Waterloo], University of Maryland School of Medicine, University of Maryland System, Institut National de l'Environnement Industriel et des Risques (INERIS), Institute of Pop. Genetics, CNR, Sassari, Interfaculty Institute for Genetics and Functional Genomics, Universität Greifswald - University of Greifswald, IT University of Copenhagen (ITU), Robertson Centre for Biostatistics, University of Glasgow, Centre for Causal Analyses in Translational Epidemiology, University of Bristol [Bristol]-Medical Research Council, King‘s College London, Jinan University [Guangzhou], Institute of Oceanology [China], School Medicine, University of Pittsburgh (PITT), Pennsylvania Commonwealth System of Higher Education (PCSHE)-Pennsylvania Commonwealth System of Higher Education (PCSHE), General Internal Medicine, Johns Hopkins School of Medicine, Johns Hopkins University School of Medicine [Baltimore], Shardna life science Pula Cagliari, Section Molecular Epidemiology, Leiden University Medical Center (LUMC), Department of Medicine, University of Eastern Finland-Kuopio University Hospital, Medstar Research Institute, Department of Cardiology, Ernst-Moritz-Arndt University, Center for Biological Sequence Analysis [Lyngby], Danmarks Tekniske Universitet = Technical University of Denmark (DTU), Department of Internal Medicine, University of Groningen and University Medical Center Groningen, Department of Epidemiology, Harvard School of Public Health, German Research Center for Environmental Health - Helmholtz Center München (GmbH), Metacohorts Consortium, INEOS Technologies (SWITZERLAND), MRC Epidemiology Unit, University of Cambridge [UK] (CAM)-Institute of Metabolic Science, University of Edinburgh, School of Population Health [Crawley, Western Australia], The University of Western Australia (UWA), Institute of Genetics and Biophysics, National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), The Scripps Translational Science Institute and Scripps Health, Tulane Center for Cardiovascular Health, Tulane University Health Sciences Center, Centre for Population Health Sciences, Genomic Research Laboratory, Service of Infectious Disease, Hôpitaux Universitaires de Genève (HUG), Infectious diseases division, Department of internal medicine, Washington University in Saint Louis (WUSTL), Luleå University of Technology (LUT), Recherche en épidémiologie et biostatistique, Université Paris-Sud - Paris 11 (UP11)-Institut National de la Santé et de la Recherche Médicale (INSERM), Austrian Institute of Technology [Vienna] (AIT), Icahn School of Medicine at Mount Sinai [New York] (MSSM), Department of Rheumatology and Clinical Epidemiology, Leiden University Medical Center (LUMC), Department of Rheumatology and Clinical Epidemiology [Leiden University Medical Center] (LUMC), Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden-Leiden University Medical Center (LUMC), Universiteit Leiden-Universiteit Leiden, Department of Biostatistics and Center for Statistical Genetics, University of Michigan [Ann Arbor], University of Michigan System-University of Michigan System, University of Virginia, Tampere University Hospital, Department of Medical Genetics, Université de Lausanne = University of Lausanne (UNIL), Department of Pathological Biochemistry, Royal Infirmary, Oxford University, University of Oxford, University of Newcastle [Callaghan, Australia] (UoN), Department of neurology, Institute of Metabolic Science, MRC, The Wellcome Trust Centre for Human Genetics [Oxford], Uppsala Universitet [Uppsala], QIMR Berghofer Medical Research Institute, Institute of Genetic Epidemiology [Neuherberg, Germany], Institute of Human Genetics, Helmholtz Zentrum München = German Research Center for Environmental Health, Schizophrenia Research Institute [Sydney], Department of Genetics, University of North Carolina System (UNC)-University of North Carolina System (UNC), Vrije Universiteit Brussel (VUB), Population Health Sciences and Education, St George's University of London, Centre Hospitalier Universitaire Vaudois [Lausanne] (CHUV), Institute of Health Sciences and Biocenter Oulu, University of Oulu, Medizinische Klinik und Poliklinik, Johannes Gutenberg - Universität Mainz = Johannes Gutenberg University (JGU), Institute of Clinical Chemistry and Laboratory Medicine, Icelandic Heart Association, Heart Preventive Clinic and Research Institute, Departments of Epidemiology and Nutrition, Institute of Epidemiology [Neuherberg] (EPI), Medical University Graz, Transplantation Laboratory [Helsinki], Haartman Institute [Helsinki], Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Faculty of Medecine [Helsinki], Helsingin yliopisto = Helsingfors universitet = University of Helsinki-Helsingin yliopisto = Helsingfors universitet = University of Helsinki, Department of Chronic Disease Prevention, National Institute for Health and Welfare [Helsinki], Dept. of Epidemiology Research, Statens Serum Institut [Copenhagen], CLinical Psychology, Genetics and Pathology, Geriatric Rehabilitation Unit, Azienda Sanitaria Firenze, Center For Narcolepsy, Stanford University, Centre for Bone and Arthritis Research, University of Gothenburg (GU)-Institute of Medicine, MRC Human Gentics Unit, Inst Genet and Mol Med, Western General Hospital, Edinburgh, University of Maryland School of Medicine [Baltimore, MD, USA], Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Department of Physics [Stockholm], Stockholm University, University of Bristol [Bristol], Universiteit Leiden, Department of Epidemiology, University of Washington, University of Washington [Seattle], Department of Epidemiology [Rotterdam], University of Groningen [Groningen], Dutch Initiative on Crohn and Colitis (ICC), Icelandic Heart Association [Kopavogur, Iceland] (IHA), Department of Physiology and Biophysics [Jackson, MS, USA], University of Southern Mississippi (USM), Human Genetics Branch, National Institutes of Health [Bethesda] (NIH)-National Institute of Mental Health (NIMH), Faculty of Medicine and Life Sciences [Tampere], University of Tampere [Finland], German Center for Cardiovascular Research (DZHK), Berlin Institute of Health (BIH), MRC Centre for Neuropsychiatric Genetics and Genomics, Medical Research Council-Cardiff University, Department of Social Medicine, School of Medicine [Los Angeles], University of California [Los Angeles] (UCLA), University of California (UC)-University of California (UC), Department of Medicine [Aurora, CO, USA], University of Colorado [Denver], Institute for Molecular Medicine Finland [Helsinki] (FIMM), Helsinki Institute of Life Science (HiLIFE), Mathematical Institute [Oxford] (MI), Institute of Psychiatry, Psychology & Neuroscience, King's College London, LifeLines Cohort Study, CHARGE Inflammation Working Group, Ligthart, S., Vaez, A., Vosa, U., Stathopoulou, M. G., de Vries, P. S., Prins, B. P., Van der Most, P. J., Tanaka, T., Naderi, E., Rose, L. M., Wu, Y., Karlsson, R., Barbalic, M., Lin, H., Pool, R., Zhu, G., Mace, A., Sidore, C., Trompet, S., Mangino, M., Sabater-Lleal, M., Kemp, J. P., Abbasi, A., Kacprowski, T., Verweij, N., Smith, A. V., Huang, T., Marzi, C., Feitosa, M. F., Lohman, K. K., Kleber, M. E., Milaneschi, Y., Mueller, C., Huq, M., Vlachopoulou, E., Lyytikainen, L. -P., Oldmeadow, C., Deelen, J., Perola, M., Zhao, J. H., Feenstra, B., Alizadeh, B. Z., Boezen, H. M., Franke, L., van der Harst, P., Navis, G., Rots, M., Snieder, H., Swertz, M., Wolffenbuttel, B. H. R., Wijmenga, C., Amini, M., Benjamin, E., Chasman, D. I., Dehghan, A., Ahluwalia, T. S., Meigs, J., Tracy, R., Bis, J., Eiriksdottir, G., Pankratz, N., Gross, M., Rainer, A., Wilson, J. G., Psaty, B. M., Dupuis, J., Prins, B., Vaso, U., Stathopoulou, M., Lehtimaki, T., Koenig, W., Jamshidi, Y., Siest, S., Uitterlinden, A. G., Abdollahi, M., Schnabel, R., Schick, U. M., Nolte, I. M., Kraja, A., Hsu, Y. -H., Tylee, D. S., Zwicker, A., Uher, R., Davey-Smith, G., Morrison, A. C., Hicks, A., van Duijn, C. M., Ward-Caviness, C., Boerwinkle, E., Rotter, J., Rice, K., Lange, L., de Geus, E., Morris, A. P., Makela, K. M., Stacey, D., Eriksson, J., Frayling, T. M., Slagboom, E. P., Lahti, J., Schraut, K. E., Fornage, M., Suktitipat, B., Chen, W. -M., Li, X., Nutile, T., Malerba, G., Luan, J., Bak, T., Schork, N., Del Greco, M. F., Thiering, E., Mahajan, A., Marioni, R. E., Mihailov, E., Ozel, A. B., Zhang, W., Nethander, M., Cheng, Y. -C., Aslibekyan, S., Ang, W., Gandin, I., Yengo, L., Portas, L., Kooperberg, C., Hofer, E., Rajan, K. B., Schurmann, C., den Hollander, W., Zhao, J., Draisma, H. H. M., Ford, I., Timpson, N., Teumer, A., Huang, H., Wahl, S., Liu, Y., Huang, J., Uh, H. -W., Geller, F., Joshi, P. K., Yanek, L. R., Trabetti, E., Lehne, B., Vozzi, D., Verbanck, M., Biino, G., Saba, Y., Meulenbelt, I., O'Connell, J. R., Laakso, M., Giulianini, F., Magnusson, P. K. E., Ballantyne, C. M., Hottenga, J. J., Montgomery, G. W., Rivadineira, F., Rueedi, R., Steri, M., Herzig, K. -H., Stott, D. J., Menni, C., Franberg, M., S, t. Pourcain B., Felix, S. B., Pers, T. H., Bakker, S. J. L., Kraft, P., Peters, A., Vaidya, D., Delgado, G., Smit, J. H., Grossmann, V., Sinisalo, J., Seppala, I., Williams, S. R., Holliday, E. G., Moed, M., Langenberg, C., Raikkonen, K., Ding, J., Campbell, H., Sale, M. M., Chen, Y. -D. I., James, A. L., Ruggiero, D., Soranzo, N., Hartman, C. A., Smith, E. N., Berenson, G. S., Fuchsberger, C., Hernandez, D., Tiesler, C. M. T., Giedraitis, V., Liewald, D., Fischer, K., Mellstrom, D., Larsson, A., Wang, Y., Scott, W. R., Lorentzon, M., Beilby, J., Ryan, K. A., Pennell, C. E., Vuckovic, D., Balkau, B., Concas, M. P., Schmidt, R., Mendes de Leon, C. F., Bottinger, E. P., Kloppenburg, M., Paternoster, L., Boehnke, M., Musk, A. W., Willemsen, G., Evans, D. M., Madden, P. A. F., Kahonen, M., Kutalik, Z., Zoledziewska, M., Karhunen, V., Kritchevsky, S. B., Sattar, N., Lachance, G., Clarke, R., Harris, T. B., Raitakari, O. T., Attia, J. R., van Heemst, D., Kajantie, E., Sorice, R., Gambaro, G., Scott, R. A., Hicks, A. A., Ferrucci, L., Standl, M., Lindgren, C. M., Starr, J. M., Karlsson, M., Lind, L., Li, J. Z., Chambers, J. C., Mori, T. A., de Geus, E. J. C. N., Heath, A. C., Martin, N. G., Auvinen, J., Buckley, B. M., de Craen, A. J. M., Waldenberger, M., Strauch, K., Meitinger, T., Scott, R. J., Mcevoy, M., Beekman, M., Bombieri, C., Ridker, P. M., Mohlke, K. L., Pedersen, N. L., Boomsma, D. I., Whitfield, J. B., Strachan, D. P., Hofman, A., Vollenweider, P., Cucca, F., Jarvelin, M. -R., Jukema, J. W., Spector, T. D., Hamsten, A., Zeller, T., Nauck, M., Gudnason, V., Qi, L., Grallert, H., Borecki, I. B., Rotter, J. I., Marz, W., Wild, P. S., Lokki, M. -L., Boyle, M., Salomaa, V., Melbye, M., Eriksson, J. G., Wilson, J. F., Penninx, B. W. J. H., Becker, D. M., Worrall, B. B., Gibson, G., Krauss, R. M., Ciullo, M., Zaza, G., Wareham, N. J., Oldehinkel, A. J., Palmer, L. J., Murray, S. S., Pramstaller, P. P., Bandinelli, S., Heinrich, J., Ingelsson, E., Deary, I. J., Magi, R., Vandenput, L., Desch, K. C., Kooner, J. S., Ohlsson, C., Hayward, C., Shuldiner, A. R., Arnett, D. K., Beilin, L. J., Robino, A., Froguel, P., Pirastu, M., Jess, T., Loos, R. J. F., Evans, D. A., Schmidt, H., Slagboom, P. E., Tracy, R. P., Visvikis-Siest, S., Reiner, A. P., Bis, J. C., Franco, O. H., Benjamin, E. J., AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Graduate School, Epidemiology, Internal Medicine, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Stem Cell Aging Leukemia and Lymphoma (SALL), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), VU University medical center, Psychiatry, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Methodology, APH - Digital Health, Biological Psychology, APH - Personalized Medicine, APH - Health Behaviors & Chronic Diseases, Universität Heidelberg [Heidelberg], University of Verona (UNIVR), Department of Molecular and Experimental Medicine, The Scripps Research Institute, The Scripps Research Institute, Université Grenoble Alpes - UFR Sciences de l'Homme et de la Société (UGA UFR SHS), Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), IT University of Copenhagen, Technical University of Denmark [Lyngby] (DTU), Consiglio Nazionale delle Ricerche (CNR), University of Virginia [Charlottesville], Université de Lausanne (UNIL), University of Oxford [Oxford], University of Newcastle [Australia] (UoN), Centre d'économie industrielle i3 (CERNA i3), Centre National de la Recherche Scientifique (CNRS)-MINES ParisTech - École nationale supérieure des mines de Paris, Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL), Helmholtz-Zentrum München (HZM), Laboratoire Interuniversitaire des Systèmes Atmosphériques (LISA (UMR_7583)), Institut national des sciences de l'Univers (INSU - CNRS)-Université Paris Diderot - Paris 7 (UPD7)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Centre National de la Recherche Scientifique (CNRS), Universitätsmedizin der Johannes-Gutenberg Universität Mainz, University of Helsinki-University of Helsinki-Faculty of Medecine [Helsinki], University of Helsinki-University of Helsinki, Cardiff University-Medical Research Council, University of California-University of California, and DE CARVALHO, Philippe
Subjects: 0301 basic medicine, Male, Netherlands Twin Register (NTR), Bipolar Disorder, LD SCORE REGRESSION, [SDV]Life Sciences [q-bio], Genome-wide association study, [SDV.GEN] Life Sciences [q-bio]/Genetics, Body Mass Index, inflammatory disorder, 80 and over, WIDE ASSOCIATION, EPIDEMIOLOGY, ta318, International HapMap Project, Child, Genetics (clinical), 2. Zero hunger, Genetics, Genetics & Heredity, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, C-reactive proteingenome-wide association studyinflammationMendelian randomizationinflammatory disordersDEPICTcoronary artery diseaseschizophreniasystem biology, system biology, DEPICT, Mendelian Randomization Analysis, 11 Medical And Health Sciences, Middle Aged, C-reactive protein, coronary artery disease, genome-wide association study, inflammation, inflammatory disorders, Mendelian randomization, schizophrenia, Adolescent, Adult, Aged, Biomarkers, C-Reactive Protein, Female, Genetic Loci, Genome-Wide Association Study, Humans, Inflammation, Liver, Metabolic Networks and Pathways, Schizophrenia, Young Adult, 3. Good health, [SDV] Life Sciences [q-bio], Medical genetics, Biomarker (medicine), Life Sciences & Biomedicine, Human, medicine.medical_specialty, CHARGE Inflammation Working Group, Biology, IMMUNITY, ta3111, Article, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, CORONARY-HEART-DISEASE, Mendelian Randomization Analysi, 1000 Genomes Project, METAANALYSIS, Genetic association, [SDV.GEN]Life Sciences [q-bio]/Genetics, Science & Technology, ta1184, Metabolic Networks and Pathway, Biomarker, INSTRUMENTS, 06 Biological Sciences, 030104 developmental biology, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, LifeLines Cohort Study
Abstract: International audience; C-reactive protein (CRP) is a sensitive biomarker of chronic low-grade inflammation and is associated with multiple complex diseases. The genetic determinants of chronic inflammation remain largely unknown, and the causal role of CRP in several clinical outcomes is debated. We performed two genome-wide association studies (GWASs), on HapMap and 1000 Genomes imputed data, of circulating amounts of CRP by using data from 88 studies comprising 204,402 European individuals. Additionally, we performed in silico functional analyses and Mendelian randomization analyses with several clinical outcomes. The GWAS meta-analyses of CRP revealed 58 distinct genetic loci (p < 5 × 10-8). After adjustment for body mass index in the regression analysis, the associations at all except three loci remained. The lead variants at the distinct loci explained up to 7.0% of the variance in circulating amounts of CRP. We identified 66 gene sets that were organized in two substantially correlated clusters, one mainly composed of immune pathways and the other characterized by metabolic pathways in the liver. Mendelian randomization analyses revealed a causal protective effect of CRP on schizophrenia and a risk-increasing effect on bipolar disorder. Our findings provide further insights into the biology of inflammation and could lead to interventions for treating inflammation and its clinical consequences.Copyright © 2018 American Society of Human Genetics. All rights reserved.
Published: 2018

25. Corrigendum to 'Long-term course of negative symptom subdomains and relationship with outcome in patients with a psychotic disorder' [Schizophr. Res. 193 (2018) 173-181]

Author: Annemarie P.M. Stiekema, Md Atiqul Islam, Edith J. Liemburg, Stynke Castelein, Edwin R. van den Heuvel, Jaap van Weeghel, André Aleman, Richard Bruggeman, Lisette van der Meer, Behrooz Z. Alizadeh, Agna A. Bartels-Velthuis, Nico J. van Beveren, Wiepke Cahn, Lieuwe de Haan, Philippe Delespaul, Carin J. Meijer, Inez Myin-Germeys, Rene S. Kahn, Frederike Schirmbeck, Claudia J.P. Simons, Neeltje E.M. van Haren, Jim van Os, and Ruud van Winkel
Subjects: Negative symptom, Psychiatry and Mental health, Clinical psychiatry, medicine.medical_specialty, Child and adolescent psychiatry, medicine, Library science, Mental health care, University medical, Center (algebra and category theory), In patient, Psychology, Biological Psychiatry
Abstract: The authors regret that the GROUP-investigators were not acknowledged for their work due to a missing affiliation in the original publication. The new authorship line is: Annemarie P.M. Stiekema a,b Md Atiqul Islam c,d,e Edith J. Liemburg c,d,f Stynke Castelein c,g Edwin R. van den Heuvel h Jaap van Weeghel i,j Andre Aleman f,k Richard Bruggeman c,d Lisette van der Meer a,c GROUP-investigators l a Lentis Psychiatric Institute, Department of Rehabilitation, Zuidlaren, The Netherlands b School for Mental Health and Neuroscience, Faculty of Health, Medicine and Life Sciences, Maastricht University Medical Centre, Maastricht, The Netherlands c University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Groningen, The Netherlands d University of Groningen, University Medical Center Groningen, Groningen, Rob Giel Research center, The Netherlands e Department of Statistics, Shahjalal University of Science and Technology, Sylhet 3114, Bangladesh f University of Groningen, University Medical Center Groningen, Department of Neuroscience, Groningen, The Netherlands g Lentis Psychiatric Institute, Research Department, Groningen, The Netherlands h Department of Mathematics and Computer Science, Eindhoven University of Technology, Eindhoven, The Netherlands i Parnassia Group, Dijk en Duin Mental Health Center, Castricum, The Netherlands j Department of TRANZO, Tilburg School of Social and Behavioral Sciences, Tilburg University, The Netherlands k University of Groningen, Department of Clinical Psychology and Experimental Psychopathology, Groningen, The Netherlands l GROUP investigators are: Behrooz Z. Alizadeh m , Agna A. Bartels-Velthuis n , Nico J. van Beveren o,p,q , Richard Bruggeman n , Wiepke Cahn r , Lieuwe de Haan s , Philippe Delespaul t , Carin J. Meijer s , Inez Myin-Germeys u , Rene S. Kahn r , Frederike Schirmbeck s , Claudia J.P. Simons t,v , Neeltje E.M. van Haren r,w , Jim van Os t,x , Ruud van Winkel u m University of Groningen, University Medical Center Groningen, Department of Epidemiology, Groningen, The Netherlands n University of Groningen, University Medical Center Groningen, University Center for Psychiatry, Rob Giel Research center, Groningen, The Netherlands o Antes Center for Mental Health Care, Rotterdam, The Netherlands p Erasmus MC, Department of Psychiatry, Rotterdam, The Netherlands q Erasmus MC, Department of Neuroscience, Rotterdam, The Netherlands r University Medical Center Utrecht, Department of Psychiatry, Brain Centre Rudolf agnus, Utrecht, The Netherlands s Academic Medical Center, University of Amsterdam, Department of Psychiatry, Amsterdam, The Netherlands t Maastricht University Medical Center, Department of Psychiatry and Neuropsychology, School for Mental Health and Neuroscience, Maastricht, The Netherlands u KU Leuven, Department of Neuroscience, Research Group Psychiatry, Center for Clinical Psychiatry, Leuven, Belgium v GGzE, Institute for Mental Health Care Eindhoven and De Kempen, Eindhoven, The Netherlands w Department of Child and Adolescent Psychiatry/Psychology, Erasmus Medical Centre, Rotterdam, Netherlands x King's College London, King's Health Partners, Department of Psychosis Studies, Institute of Psychiatry, London, United Kingdom The authors apologise for any inconvenience caused.
Published: 2019

26. P749 Early environmental and lifestyle factors are associated with developing inflammatory bowel disease

Author: K. W. J. Van der Sloot, Behrooz Z. Alizadeh, Rinse K. Weersma, and Gerard Dijkstra
Subjects: medicine.medical_specialty, Lifestyle factors, business.industry, Internal medicine, Gastroenterology, Medicine, General Medicine, business, medicine.disease, Inflammatory bowel disease
Published: 2019

27. Bilirubin as a Potential Causal Factor in Type 2 Diabetes Risk: A Mendelian Randomization Study

Author: Behrooz Z. Alizadeh, Stephan J. L. Bakker, Ronald P. Stolk, Petronella E. Deetman, Rijk O. B. Gans, Pim van der Harst, Hans L. Hillege, Eva Corpeleijn, Gerjan Navis, Ron T. Gansevoort, Ali Abbasi, Reproductive Origins of Adult Health and Disease (ROAHD), Lifestyle Medicine (LM), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), Vascular Ageing Programme (VAP), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Value, Affordability and Sustainability (VALUE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Adult, Male, medicine.medical_specialty, Genotype, Bilirubin, Endocrinology, Diabetes and Metabolism, HEART-DISEASE, Type 2 diabetes, Biology, Lower risk, Polymorphism, Single Nucleotide, Gastroenterology, Article, GLUCOSE, chemistry.chemical_compound, Diabetes mellitus, Internal medicine, Mendelian randomization, Internal Medicine, medicine, Humans, Genetic Predisposition to Disease, Glucuronosyltransferase, GENOME-WIDE ASSOCIATION, OXIDATIVE STRESS, Prospective cohort study, Alleles, Aged, METABOLIC SYNDROME, HYPERBILIRUBINEMIA, MORTALITY, COMMON VARIANTS, Mendelian Randomization Analysis, Odds ratio, Middle Aged, medicine.disease, MULTIPLE GENETIC-VARIANTS, Endocrinology, Diabetes Mellitus, Type 2, chemistry, SERUM BILIRUBIN, Female
Abstract: Circulating bilirubin, a natural antioxidant, is associated with decreased risk of type 2 diabetes (T2D), but the nature of the relationship remains unknown. We performed Mendelian randomization in a prospective cohort of 3,381 participants free of diabetes at baseline (age 28–75 years; women 52.6%). We used rs6742078 located in the uridine diphosphate–glucuronosyltransferase locus as an instrumental variable (IV) to study a potential causal effect of serum total bilirubin level on T2D risk. T2D developed in a total of 210 participants (6.2%) during a median follow-up period of 7.8 years. In adjusted analyses, rs6742078, which explained 19.5% of bilirubin variation, was strongly associated with total bilirubin (a 0.68-SD increase in bilirubin levels per T allele; P < 1 × 10−122) and was also associated with T2D risk (odds ratio [OR] 0.69 [95% CI 0.54–0.90]; P = 0.006). Per 1-SD increase in log-transformed bilirubin levels, we observed a 25% (OR 0.75 [95% CI 0.62–0.92]; P = 0.004) lower risk of T2D. In Mendelian randomization analysis, the causal risk reduction for T2D was estimated to be 42% (causal OR for IV estimation per 1-SD increase in log-transformed bilirubin 0.58 [95% CI 0.39–0.84]; P = 0.005), which was comparable to the observational estimate (Durbin-Wu-Hausman χ2 test, P for difference = 0.19). These novel results provide evidence that an elevated bilirubin level is causally associated with the risk of T2D and support its role as a protective determinant.
Published: 2014

28. Prevalence and determinants of non-alcoholic fatty liver disease in lifelines: A large Dutch population cohort

Author: Tim C. M. A. Schreuder, Klaas Nico Faber, Robin P. F. Dullaart, Marzyeh Amini, Behrooz Z. Alizadeh, Eline H. van den Berg, Hans Blokzijl, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Life Course Epidemiology (LCE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: 0301 basic medicine, Male, Cirrhosis, lcsh:Medicine, Gastroenterology, Biochemistry, GLOMERULAR-FILTRATION-RATE, STEATOHEPATITIS, White Blood Cells, 0302 clinical medicine, Endocrinology, Non-alcoholic Fatty Liver Disease, Risk Factors, Animal Cells, Prevalence, Medicine and Health Sciences, Diabetes diagnosis and management, lcsh:Science, Netherlands, METABOLIC SYNDROME, 2. Zero hunger, INSULIN-RESISTANCE, Multidisciplinary, Liver Diseases, Fatty liver, Middle Aged, Lipids, 3. Good health, Type 2 Diabetes, Cholesterol, Hypertension, 030211 gastroenterology & hepatology, Female, Anatomy, Cellular Types, Research Article, Adult, medicine.medical_specialty, HbA1c, Endocrine Disorders, Immune Cells, Immunology, UNITED-STATES, Gastroenterology and Hepatology, 03 medical and health sciences, Insulin resistance, Internal medicine, Diabetes mellitus, medicine, Diabetes Mellitus, Humans, Hemoglobin, HEPATIC STEATOSIS, Hepatitis, Blood Cells, business.industry, Cholesterol, HDL, lcsh:R, Type 2 Diabetes Mellitus, Biology and Life Sciences, Proteins, Renal System, Cell Biology, medicine.disease, Diagnostic medicine, Fatty Liver, SERUM CREATININE VALUES, RENAL-DISEASE, 030104 developmental biology, Cross-Sectional Studies, Diabetes Mellitus, Type 2, ATHEROSCLEROSIS, Hyperglycemia, Metabolic Disorders, RISK-FACTORS, lcsh:Q, Steatohepatitis, Metabolic syndrome, business
Abstract: BACKGROUND & AIMS Non-alcoholic fatty liver disease is an increasing health issue that develops rather unnoticed with obesity, type 2 diabetes mellitus and metabolic syndrome. We investigated prevalence, determinants and associated metabolic abnormalities of non-alcoholic fatty liver disease in the largest population-based cohort to date. METHODS Biochemical characteristics, type 2 diabetes mellitus and metabolic syndrome were determined in the Lifelines Cohort Study (N = 167,729), a population-based cohort in the North of the Netherlands. Non-alcoholic fatty liver disease was defined as Fatty Liver Index (FLI)≥60. Exclusion criteria were age
Published: 2017

29. P815 How to measure environmental exposures (the exposome) in inflammatory bowel disease?

Author: Behrooz Z. Alizadeh, Gerard Dijkstra, and K. W. J. Van der Sloot
Subjects: medicine.medical_specialty, Exposome, business.industry, Internal medicine, Gastroenterology, medicine, Measure (physics), General Medicine, medicine.disease, business, Inflammatory bowel disease
Published: 2018

30. OC-0494 Genetic variants associated with radiationinduced xerostomia in head and neck cancer: a GWA study

Author: Henk P. Bijl, M. Dieters, Behrooz Z. Alizadeh, Elnaz Naderi, M Boezen, Roel J H M Steenbakkers, Johannes A. Langendijk, Anne P G Crijns, and J. F. Van den Hoek
Subjects: Oncology, medicine.medical_specialty, business.industry, Internal medicine, Head and neck cancer, medicine, Genetic variants, Radiology, Nuclear Medicine and imaging, Hematology, Radiation-induced xerostomia, business, medicine.disease
Published: 2019

31. SU129TYPE 2 DIABETES MELLITUS IN PATIENTS WITH SCHIZOPHRENIA: THE EFFECT OF (POLY)GENETIC RISK SCORE OF SCHIZOPHRENIA AND TYPE 2 DIABETES AND ANTIPSYCHOTIC MEDICATION USE

Author: Edith J. Liemburg, Md. Atiqul Islam, Behrooz Z. Alizadeh, Tesfa Dejenie Habtewold, and Richard Bruggeman
Subjects: Pharmacology, medicine.medical_specialty, Medication use, business.industry, medicine.medical_treatment, Type 2 Diabetes Mellitus, Type 2 diabetes, medicine.disease, Psychiatry and Mental health, Neurology, Schizophrenia, Internal medicine, Medicine, Pharmacology (medical), In patient, Neurology (clinical), Genetic risk, business, Antipsychotic, Biological Psychiatry
Published: 2019

32. Neglected role of hookah and opium in gastric carcinogenesis: A cohort study on risk factors and attributable fractions

Author: Farhad Pourfarzi, Masoomeh Alimohammadian, Mohammad H. Derakhshan, Reza Malekzadeh, Behrooz Z. Alizadeh, Arash Nikmanesh, Fatemeh Samadi, Geertruida H. de Bock, Majid Boreiri, Alireza Delavari, Mahbubeh Parsaeian, Masoud Babaei, Abbas Yazdanbod, Farhad Islami, Emad Ahmadi, Farshad Farzadfar, Masoud Sotoudeh, Alireza Sadjadi, and Arash Etemadi
Subjects: Cancer Research, medicine.medical_specialty, education.field_of_study, biology, Atrophic gastritis, business.industry, Population, Opium, Cancer, Odds ratio, Helicobacter pylori, medicine.disease, biology.organism_classification, Gastroenterology, Oncology, Internal medicine, medicine, Salt intake, education, business, medicine.drug, Cohort study
Abstract: A recent study showed an association between hookah/opium use and gastric cancer but no study has investigated the relationship with gastric precancerous lesions. We examined the association between hookah/opium and gastric precancerous lesions and subsequent gastric cancer. In a population-based cohort study, 928 randomly selected, healthy, Helicobacter pylori-infected subjects in Ardabil Province, Iran, were followed for 10 years. The association between baseline precancerous lesions and lifestyle risk factors (including hookah/opium) was analyzed using logistic regression and presented as odds ratios (ORs) and 95% confidence intervals (CIs). We also calculated hazard ratios (HRs) and 95% CIs for the associations of lifestyle risk factors and endoscopic and histological parameters with incident gastric cancers using Cox regression models. Additionally, the proportion of cancers attributable to modifiable risk factors was calculated. During 9,096 person-years of follow-up, 36 new cases of gastric cancer were observed (incidence rate: 3.96/1,000 persons-years). Opium consumption was strongly associated with baseline antral (OR: 3.2; 95% CI: 1.2-9.1) and body intestinal metaplasia (OR: 7.3; 95% CI: 2.5-21.5). Opium (HR: 3.2; 95% CI: 1.4-7.7), hookah (HR: 3.4; 95% CI: 1.7-7.1) and cigarette use (HR: 3.2; 95% CI: 1.4-7.5), as well as high salt intake, family history of gastric cancer, gastric ulcer and histological atrophic gastritis and intestinal metaplasia of body were associated with higher risk of gastric cancer. The fraction of cancers attributable jointly to high salt, low fruit intake, smoking (including hookah) and opium was 93% (95% CI: 83-98). Hookah and opium use are risk factors for gastric cancer as well as for precancerous lesions. Hookah, opium, cigarette and high salt intake are important modifiable risk factors in this high-incidence gastric cancer area.
Published: 2013

33. Prevalence of non-alcoholic fatty liver disease and fibrosis in a large population cohort in the north of the Netherlands: A lifelines cohort study

Author: Hans Blokzijl, E. van den Berg, Klaas Nico Faber, T.C.M.A. Schreuder, Robin P. F. Dullaart, Marzyeh Amini, Behrooz Z. Alizadeh, Lifestyle Medicine (LM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Center for Liver, Digestive and Metabolic Diseases (CLDM), Life Course Epidemiology (LCE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: 0301 basic medicine, Pathology, leukocyte count, obesity, Cirrhosis, cholesterol blood level, population, epidemic, low density lipoprotein cholesterol, 0302 clinical medicine, health behavior, high density lipoprotein cholesterol, rank sum test, Medicine, hepatitis, glucose, hemoglobin A1c, Netherlands, liver fibrosis, statistical significance, education.field_of_study, medicine.diagnostic_test, Fatty liver, health, cohort analysis, waist circumference, female, Cohort, history, triacylglycerol, diet restriction, Cohort study, medicine.medical_specialty, liver cirrhosis, alcohol consumption, Population, prevalence, 030209 endocrinology & metabolism, liver, European, Student t test, 03 medical and health sciences, statistical analysis, male, lipid, Internal medicine, nonalcoholic fatty liver, liver function test, human, education, fatty liver, Hepatitis, Hepatology, business.industry, fibrosis, nutritional and metabolic diseases, hemoglobin, medicine.disease, 030104 developmental biology, metabolic syndrome X, Metabolic syndrome, business, Liver function tests, chi square test
Abstract: Background and Aims: Non-alcoholic fatty liver disease (NAFLD) is an increasing health issue, being part of the worldwide epidemic of obesity. The aim of this study was to investigate the prevalence of NAFLD and fibrosis and analyze biochemical characteristics in a large population-based cohort study. Methods: The study was conducted in the framework of the LifeLines Cohort, a population-based cohort study examining the health and health-related behaviours of participants living in the Northern region of the Netherlands (n = 167,000), of which 57,682 participants older than 18 years with available biomedical data were eligible. A priori-defined liver function tests, lipid profile, leukocyte count, CRP, haemoglobin A1c (HbA1c) and fasting glucose (FG) were studied. NAFLD was defined by using the validated Fatty Liver Index (FLI); FLI ≥ 60 was categorized as NAFLD. Advanced liver fibrosis (stages 3/ 4) was defined by using the validated NAFLD Fibrosis Score; a score >0.676 was categorized as fibrosis. Exclusion criteria were non-Dutch participants, participants with missing data, excessive alcohol use and previous diagnosed hepatitis and/or cirrhosis. Statistical analysis included t test, Mann-Whitney U test and Chi-square test when applicable. A p-value 0.676, indicative of significant fibrosis, was found in 223 (0.6%) participants. Conclusions: NAFLD is a potential health problem in the Northern part of the Netherlands; 22% of the population is suspected of having NAFLD which is associated with the metabolic syndrome and inflammatory indices. Even more, 223 participants were suspected to suffer from advanced liver fibrosis. Future validation and population-based studies are mandatory to better understand the natural history of NAFLD and prevent its complications.
Published: 2016

34. Cannabis and a lower BMI in psychosis: What is the role of AKT1?

Author: Nico J.M. van Beveren, Md. Atiqul Islam, L. de Haan, Durk Wiersma, Edith J. Liemburg, Richard Bruggeman, Jojanneke Bruins, Carin J. Meijer, R.S. Kahn, Behrooz Z. Alizadeh, I. Myin-Germeys, Wiepke Cahn, J. van Os, ANS - Mood, Anxiety, Psychosis, Stress & Sleep, Adult Psychiatry, Psychiatry, PharmacoTherapy, -Epidemiology and -Economics, Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Male, Psychotic disorder, GLUCOSE, Body Mass Index, 0302 clinical medicine, Risk Factors, Longitudinal Studies, METABOLIC SYNDROME, biology, Incidence (epidemiology), Middle Aged, Psychiatry and Mental health, GENOTYPE INFLUENCES, Body mass, Schizophrenia, embryonic structures, Regression Analysis, Female, Marijuana Use, ENERGY-BALANCE, Biological psychiatry, Psychology, MENTAL-HEALTH, Adult, Psychosis, medicine.medical_specialty, Adolescent, Single-nucleotide polymorphism, ILLNESS, Polymorphism, Single Nucleotide, 03 medical and health sciences, Young Adult, Internal medicine, medicine, Genetics, Journal Article, Humans, Genetic Predisposition to Disease, Psychiatry, Biological Psychiatry, Alleles, Cannabis, Glycated Hemoglobin, medicine.disease, biology.organism_classification, EMERGING ROLE, 030227 psychiatry, BODY-MASS INDEX, Psychotic Disorders, Metabolic syndrome, Body mass index, Proto-Oncogene Proteins c-akt, 030217 neurology & neurosurgery
Abstract: Cannabis use has been associated with favorable outcomes on metabolic risk factors. The cause of this relation is still unknown. In this study we investigated whether this effect is mediated by the AKT1 gene, as activation of the related enzyme by cannabis may cause metabolic changes.Six Single Nucleotide Polymorphisms (SNPs) of the AKT1 gene (rs1130214, rs1130233, rs2494732, rs2498784, rs3730358, and rs3803300) of patients with psychotic disorders (n = 623) were related to Body Mass Index (BMI), levels of glycosylated hemoglobin (HBA(1c)) and total metabolic risk. Next, mediation analysis was performed with BMI as outcome, cannabis as predictor, and AKT1 as mediator. Cannabis use was inversely related to BMI but not with levels of HBA(1c) and totalmetabolic risk. Moreover, out of 6 AKT1 SNPs, rs2494732 was associated with cannabis use, but AKT1 did not mediate the effect of cannabis on BMI.In conclusion, cannabis use is likely to be associated with a lower BMI in patients with a psychotic disorder. Moreover, AKT1 risk alleles may increase the incidence of cannabis use in patients with a psychotic disorder, but AKT1 does not appear to mediate the effect of cannabis on BMI. (C) 2016 Elsevier B.V. All rights reserved.
Published: 2016

35. Eosinophil Count Is a Common Factor for Complex Metabolic and Pulmonary Traits and Diseases: The LifeLines Cohort Study

Author: Marzyeh Amini, Dinara Bashirova, Bram P Prins, Eva Corpeleijn, LifeLines Cohort Study, Marcel Bruinenberg, Lude Franke, Pim van der Harst, Gerjan Navis, Bruce H R Wolffenbuttel, Ronald P Stolk, Cisca Wijmenga, Dirkje S Postma, Gerard H Koppelman, H Marike Boezen, Judith Vonk, Harold Snieder, Behrooz Z Alizadeh, Reproductive Origins of Adult Health and Disease (ROAHD), Lifestyle Medicine (LM), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Cardiovascular Centre (CVC), Groningen Kidney Center (GKC), Life Course Epidemiology (LCE), Groningen Research Institute for Asthma and COPD (GRIAC), Value, Affordability and Sustainability (VALUE), Center for Liver, Digestive and Metabolic Diseases (CLDM), Stem Cell Aging Leukemia and Lymphoma (SALL), and Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET)
Subjects: Male, Pulmonology, Physiology, Myocardial Infarction, lcsh:Medicine, Blood Pressure, 030204 cardiovascular system & hematology, Vascular Medicine, Body Mass Index, Cohort Studies, Leukocyte Count, Pulmonary Disease, Chronic Obstructive, White Blood Cells, 0302 clinical medicine, Animal Cells, GENETIC-VARIANTS, Medicine and Health Sciences, Medicine, DIFFERENTIAL LEUKOCYTE COUNTS, lcsh:Science, Metabolic Syndrome, education.field_of_study, Multidisciplinary, Hematology, Middle Aged, Body Fluids, Blood, Physiological Parameters, Cohort, Regression Analysis, Female, Cellular Types, Anatomy, Lipoproteins, HDL, Research Article, Cohort study, Adult, medicine.medical_specialty, BLOOD-CELL COUNTS, Immune Cells, Chronic Obstructive Pulmonary Disease, Immunology, Population, Cardiology, SPUTUM EOSINOPHILS, HEART-DISEASE, AIRWAY EOSINOPHILIA, 03 medical and health sciences, FEV1/FVC ratio, Sex Factors, INFLAMMATION, Internal medicine, Humans, Obesity, education, Aged, Glycated Hemoglobin, Blood Cells, business.industry, Body Weight, lcsh:R, Biology and Life Sciences, Cell Biology, Odds ratio, medicine.disease, Asthma, Eosinophils, Blood Counts, BODY-MASS INDEX, EXACERBATIONS, Logistic Models, 030228 respiratory system, Multivariate Analysis, lcsh:Q, Metabolic syndrome, business, Body mass index, SEVERE ASTHMA
Abstract: There is ongoing debate on the association between eosinophil count and diseases, as previous studies were inconsistent. We studied the relationship of eosinophil count with 22 complex metabolic, cardiac, and pulmonary traits and diseases. From the population-based LifeLines Cohort Study (N = 167,729), 13,301 individuals were included. We focused on relationship of eosinophil count with three classes of metabolic (7 traits, 2 diseases), cardiac (6 traits, 2 diseases), and pulmonary (2 traits, 2 diseases) outcomes. Regression analyses were applied in overall, women and men, while adjusted for age, sex, BMI and smoking. A p-value of
Published: 2016

36. Association between age, IL-10, IFNγ, stimulated C-peptide and disease progression in children with newly diagnosed Type 1 diabetes

Author: C. Pfleger, Behrooz Z. Alizadeh, Henrik B. Mortensen, Bart O. Roep, A. V. Kharagjitsingh, Nanette C. Schloot, Lars Hansen, Karsten Buschard, A. Kaas, and B. P. C. Koeleman
Subjects: Type 1 diabetes, medicine.medical_specialty, C-peptide, business.industry, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Disease, medicine.disease, Gastroenterology, Pathogenesis, Interleukin 10, chemistry.chemical_compound, Endocrinology, Cytokine, chemistry, Internal medicine, Diabetes mellitus, Immunology, Internal Medicine, medicine, Interferon gamma, business, medicine.drug
Abstract: Diabet. Med. 29, 734741 (2012) Abstract Aims The relation of disease progression and age, serum interleukin 10 (IL-10) and interferon gamma (IFN?) and their genetic correlates were studied in paediatric patients with newly diagnosed Type 1 diabetes. Methods Two hundred and twenty-seven patients from the Hvidoere Study Group were classified in four different progression groups as assessed by change in stimulated C-peptide from 1 to 6 months. CA repeat variants of the IL-10 and IFN? gene were genotyped and serum levels of IL-10 and IFN? were measured at 1, 6 and 12 months. Results IL-10 decreased (P
Published: 2012

37. Trends in the utilization of invasive prenatal diagnosis in The Netherlands during 2000-2009

Author: Philip Stoutenbeek, G. Heleen Schuring-Blom, Klaske D. Lichtenbelt, Lieve Page-Christiaens, Behrooz Z. Alizadeh, P. C. J. I. Schielen, and Peter G. Scheffer
Subjects: Pediatrics, medicine.medical_specialty, Down syndrome, education.field_of_study, Pregnancy, medicine.diagnostic_test, Referral, business.industry, Population, Obstetrics and Gynecology, Chorionic villus sampling, Prenatal diagnosis, medicine.disease, Amniocentesis, medicine, Advanced maternal age, education, business, Genetics (clinical)
Abstract: OBJECTIVE: To analyze trends in the number and type of invasive procedure, reasons for referral, maternal age and chromosomal abnormalities over a 10-year period and correlate the trends to changes in the national prenatal screening policy. METHODS: Data from 10 706 invasive prenatal procedures yielding a full karyotype, performed between 2000 and 2009 were extracted from the cytogenetic database in the central region of The Netherlands. Trends were analyzed. RESULTS: Over a 10-year period, the number of invasive procedures halved and the percentage of chromosomal abnormalities detected, increased from 5.5 to 9.4%. After 2007, however, 5.7% of karyotypes in women over 36 years were found to be abnormal, versus 18.1% in women below 36 years. In 2009, 71.5% of women over 36 are still referred for invasive prenatal diagnosis on the indication advanced maternal age. CONCLUSIONS: Changes in prenatal screening policy significantly increased referral after screening and improved the efficacy of invasive prenatal diagnosis. We show the continuing effect of the different policies applied in the past to women below and above the age of 36. To further improve efficacy of invasive prenatal diagnosis, first trimester combination screening should be actively offered to women of all ages.
Published: 2011

38. Association of polymorphisms in the TLR4 gene with the risk of developing neutropenia in children with leukemia

Author: de Eveline Bont, A. P. J. de Pagter, Behrooz Z. Alizadeh, Wim J. E. Tissing, te Evelien Poele, Hendrika Boezen, Gerard H. Koppelman, Dirkje S. Postma, Karin G. E. Miedema, Willem A. Kamps, Guided Treatment in Optimal Selected Cancer Patients (GUTS), Groningen Research Institute for Asthma and COPD (GRIAC), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), and Stem Cell Aging Leukemia and Lymphoma (SALL)
Subjects: PROTOCOL, Cancer Research, medicine.medical_specialty, HYPORESPONSIVENESS, NF-KAPPA-B, Single-nucleotide polymorphism, Antineoplastic Agents, LIPOPOLYSACCHARIDE, Neutropenia, Polymorphism, Single Nucleotide, children, Internal medicine, medicine, Humans, neutropenia, Genetic Predisposition to Disease, TLR4, Risk factor, Child, ACUTE LYMPHOBLASTIC-LEUKEMIA, TOLL-LIKE RECEPTORS, GRANULOCYTE APOPTOSIS, Hematology, Leukopenia, business.industry, Cancer, Infant, Precursor Cell Lymphoblastic Leukemia-Lymphoma, INTENSIVE TREATMENT, medicine.disease, CANCER, Toll-Like Receptor 4, LIFE, Leukemia, Oncology, Child, Preschool, Immunology, Absolute neutrophil count, medicine.symptom, business, polymorphisms
Abstract: Infections are a major cause of morbidity and mortality in children with acute lymphoblastic leukemia (ALL). Susceptibility to infections increases as the neutrophil count decreases. Despite identical treatment patients vary considerably in the number of neutropenic episodes. Toll-like receptor 4 (TLR4) has been shown to have a role in inhibiting apoptosis of neutrophils. Therefore, we hypothesized that polymorphisms in the TLR4 gene may influence the number of chemotherapy-induced neutropenic episodes. Eight single-nucleotide polymorphisms (SNPs) of the TLR4 gene were determined in 194 children aged 0-17 years, who were diagnosed with ALL. We compared the genotype distributions of the SNPs with the frequency of neutropenic episodes during treatment with chemotherapeutic regimens. The number of neutropenic episodes varied from 0 to 17, with a median of four neutropenic episodes. Four SNPs in the TLR4 gene (rs10759931, rs11536889, rs1927911 and rs6478317) were associated with an increased risk of developing chemotherapy-induced neutropenia, each sustaining correction for multiple testing. Further studies are required to elucidate whether pediatric patients with ALL with the particular SNPs in the TLR4 gene also experience more infections and would benefit from prophylactic antibiotic treatment, by a reduction of morbidity and mortality due to infections.
Published: 2011

39. Fraction of diffuse gastric cancer attributable to dietary risk factors

Author: Maria Aparecida Azevedo Koike Folgueira, Priscila Abduch Branas, de Bock Gertruida H, Rodrigo Santa Cruz Guindalini, Behrooz Z. Alizadeh, and Marina Candido Visontai Cormedi
Subjects: Cancer Research, medicine.medical_specialty, Intestinal type, business.industry, Dietary risk, digestive, oral, and skin physiology, Cancer, medicine.disease, Gastroenterology, digestive system diseases, Oncology, Internal medicine, medicine, business
Abstract: e16042Background: Gastric cancer is a major health problem worldwide, especially in Brazil, where incidence rate is moderate-high. Although intestinal type of gastric cancer is clearly associated w...
Published: 2018

40. Study of the association between the CAPSL-IL7R locus and type 1 diabetes

Author: Elena Urcelay, Alfonso Martínez, E G de la Concha, Bart O. Roep, H. de la Calle, M. A. Figueredo, Jose Luis Santiago, Miguel Fernández-Arquero, B. P. C. Koeleman, Behrooz Z. Alizadeh, L. Espino, Life Course Epidemiology (LCE), Real World Studies in PharmacoEpidemiology, -Genetics, -Economics and -Therapy (PEGET), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: Male, medicine.medical_specialty, INTERLEUKIN-7, Adolescent, Genotype, Endocrinology, Diabetes and Metabolism, Population, Genome-wide association study, Single-nucleotide polymorphism, Locus (genetics), SUSCEPTIBILITY, Biology, Polymorphism, Single Nucleotide, DENDRITIC CELLS, Gastroenterology, REGION, MELLITUS, IL7R, Reference Values, Diabetes mellitus, Internal medicine, Internal Medicine, medicine, Humans, SNP, Age of Onset, GENOME-WIDE ASSOCIATION, Child, education, CAPSL, education.field_of_study, Type 1 diabetes, Receptors, Interleukin-7, diabetes, Genome, Human, medicine.disease, GENE, DEFICIENCY, Diabetes Mellitus, Type 1, Endocrinology, Cohort, Female, polymorphisms, age at onset
Abstract: Aims/hypothesis In the past few years, several genes outside the MHC region have been described as new susceptibility genetic factors to type 1 diabetes. An association between CAPSL-rs1445898 and type 1 diabetes was reported in a large white population and corroborated in a genome-wide analysis, which also found an association with IL7R, which is located adjacent to CAPSL. The aim of this study was to replicate the aforementioned associations in independent cohorts. Methods We analysed two CAPSL (rs1010601 and rs1445898) and three IL7R (rs6897932, rs987106 and rs3194051) polymorphisms. All these single nucleotide polymorphisms (SNPs) were genotyped using TaqMan minor groove binder chemistry in 301 unrelated Spanish type 1 diabetes patients and 646 healthy controls. Additionally, the associated CAPSL SNP rs1445898 was genotyped in a Dutch cohort consisting of 429 type 1 diabetes patients and 720 healthy controls. Results The homozygous mutant genotype of the CAPSL SNP rs1445898 showed a trend towards a protective effect in the overall Spanish cohort (OR [95% CI] 0.70 [0.44-1.09]; p=0.09) and in the Dutch cohort (OR [95% CI] 0.74 [0.51-1.05]; p=0.09). Pooling of both cohorts was performed, yielding a statistically significant difference (Mantel-Haenszel OR 0.71; p=0.005). This protective effect was significantly different in early-onset vs late-onset Spanish patients (OR [95% CI] 0.26 [0.10-0.65]; p=0.001). Similarly, in the early-onset subgroup, the homozygous mutant genotype of the IL7R SNP rs6897932 showed a similar protective effect (OR [95% CI] 0.18 [0.02-0.94]; p=0.02). Conclusions/interpretation In summary, we describe an independent replication of the association between the CAPSL-IL7R locus and type 1 diabetes, especially for early-onset type 1 diabetes patients.
Published: 2008

41. The association between lower educational attainment and depression owing to shared genetic effects?: Results in ~25,000 subjects

Author: Patricia A. Peyser, Jessica D. Faul, Patrik K. E. Magnusson, Nicholas D. Hastie, Beate St Pourcain, Marcus Ising, Gérard Waeber, Behrooz Z. Alizadeh, Judith M. Vonk, Lawrence F. Bielak, Sang Hong Lee, Wouter J. Peyrot, Thomas Illig, M. M. Weissman, Nicholas J. Timpson, George Dedoussis, Nicholas G. Martin, Tomi E. Mäkinen, Jorma Viikari, Lili Milani, Harold Snieder, Laura J. Bierut, A. C. Heath, Reinhold E. Schmidt, Mariza de Andrade, Vilmundur Gudnason, K. Petrovic, Robert M. Kirkpatrick, Marcela González Gross, William G. Iacono, Michelle N. Meyer, Henry Völzke, Marisa Loitfelder, Maria Dimitriou, Lude Franke, Robert F. Krueger, E. J. C. G. van den Oord, Sven Cichon, Michael Conlon O'Donovan, Ian W. Craig, Shawn N. Murphy, Danielle Posthuma, Brenda W.J.H. Penninx, Aarno Palotie, Roy Thurik, Panos Deloukas, Matt McGue, M. Preisig, Patricia A. Boyle, Osorio Meirelles, Ben A. Oostra, Klaus Berger, G. M. Montgomery, Sharon L.R. Kardia, Peter K. Joshi, K. Stefansson, Paul Lichtenstein, Andrew Heath, Andrea Schulz, Dena G. Hernandez, Debbie A Lawlor, S. P. Hamilton, James B. Potash, Z. Kutalik, Elisabeth Widen, Emil L. Sigurdsson, Rudolf S N Fehrmann, Matthias Nauck, Mikael Landén, Kurt Lohman, S.D. Gordon, Lefkos T. Middleton, Caroline Hayward, Anjali K. Henders, Philipp Koellinger, Jeffrey A. Boatman, G van Grootheest, M. Daly, Jian Yang, Peter Vollenweider, Penelope A. Lind, Stacy Steinberg, Frank J. A. van Rooij, Florian Holsboer, Hkon K. Gjessing, Erkki Vartiainen, Magnus Johannesson, Jingmei Li, David Laibson, Henrik Grönberg, Tõnu Esko, Ivana Kolcic, Niina Eklund, Kelly S. Benke, Henning Tiemeier, Isaac S. Kohane, Nicolas W. Martin, Ronny Myhre, Frans G. Zitman, Arpana Agrawal, James F. Wilson, Michael R. Barnes, Lei Yu, Thorgeir E. Thorgeirsson, Franois Bastardot, Katri Räikkönen, William Lawson, Willem A. Nolen, M. Rietschel, René Breuer, Bertram Müller-Myhsok, James A. Knowles, Grant W. Montgomery, Eva Reinmaa, Rudolf Uher, Andreas Mielck, Luigi Ferrucci, S. E. Medland, Yuri Milaneschi, Philip L. De Jager, Manfred Uhr, A. E. Farmer, Cornelia M. van Duijn, Samuli Ripatti, Marja-Liisa Nuotio, Manuel Mattheisen, Sebastian E. Baumeister, David R. Van Wagoner, Martin Preisig, Fernando Rivadeneira, Peter Lichtner, Christopher Oldmeadow, Hreinn Stefansson, Ian B. Hickie, Darina Czamara, Elizabeth G. Holliday, Astanand Jugessur, Carla A. Ibrahim-Verbaas, Jaime Derringer, Vivian S. Gainer, P. Muglia, Daniel J. Benjamin, Patrick K.E. Magnusson, Patience J. Gallagher, Jennifer A. Smith, Lynn Cherkas, Pamela A. F. Madden, David A. Bennett, Zoltán Kutalik, George Davey-Smith, Gudny Eiriksdottir, Jens Treutlein, N. Craddock, Juliette Harris, Antti Latvala, Roy H. Perlis, Markus M. Noethen, Jan-Emmanuel De Neve, Stanley I. Shyn, J.H. Smit, Dalton Conley, Adriaan Hofman, Jari Lahti, Patrick J. F. Groenen, Jüri Allik, Albert V. Smith, Ozren Polasek, Susan M. Ring, Thomas Bettecken, Michele L. Pergadia, Patrick J. McGrath, Katherine E. Tansey, Stephan Ripke, Hogni Oskarsson, Peng Lin, Douglas F. Levinson, Matthijs J. H. M. van der Loos, Melissa E. Garcia, Jonathan P. Beauchamp, Rodney J. Scott, Zhihong Zhu, Michel Guipponi, Lyle J. Palmer, Alexander Teumer, William Coryell, Stefan Kloiber, Gonneke Willemsen, John Frank, Victor M. Castro, Andrew M. McIntosh, John M. Starr, Antonio Terracciano, Mika Kähönen, Marco Masala, Markus Perola, André G. Uitterlinden, Sutapa Mukherjee, Alexander Viktorin, Lenore J. Launer, Elisabeth B. Binder, William A. Scheftner, Christel M. Middeldorp, D. H. R. Blackwood, I. Jones, Thais S. Rizzi, A. Teumer, Cornelius A. Rietveld, Aldo Rustichini, Guy Lewis, Susan L. Slager, David M. Evans, Dorret I. Boomsma, Harry Campbell, Susanne Churchill, Johan G. Eriksson, Alan F. Wright, Dan V. Iosifescu, W. Maier, Francesco Cucca, Federica Tozzi, David R. Weir, Eva Albrecht, L. Milani, Jennifer R. Harris, Min A. Jhun, Marjo-Riitta Järvelin, Martin F. Elderson, Ute Bültmann, Olli T. Raitakari, Konstantin Shakhbazov, Krista Fischer, Thomas G. Schulze, T. Jung-Ying, P. Lichtenstein, Terho Lethimäki, Jeffrey B. Weilburg, Rolf Holle, Bo Jacobsson, Pedro Marques Vidal, Jordan W. Smoller, Stavroula Kanoni, Kati Kristiansson, Sergey Goryachev, Michael Steffens, Peter M. Visscher, Toshiko Tanaka, Donald J. MacIntyre, Witte J.G. Hoogendijk, David Schlessinger, Ian J. Deary, Harm-Jan Westra, Erik Ingelsson, E.J.C. de Geus, Franziska Degenhardt, Lydia Quaye, John Barnard, David C. Liewald, John P. Rice, Christopher F. Chabris, P. McGuffin, Tamara B. Harris, C. M. Lewis, Gail Davies, Enda M. Byrne, H.-Erich Wichmann, Sara Hägg, David Cesarini, Najaf Amin, Juha Karjalainen, Dale R. Nyholt, Christian Gieger, Per Hall, Ania Korszun, Neale Bm, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Jae Hoon Sul, Christiaan de Leeuw, Antti-Pekka Sarin, Ida Surakka, Veikko Salomaa, Mina K. Chung, N. L. Pedersen, Gerome Breen, P. A. F. Madden, Martin A. Kohli, J Kaprio, John Attia, Jing Shi, Gibran Hemani, Rauli Svento, Veronique Vitart, Susanne Lucae, L. A. Jones, Jouke-Jan Hottenga, Daniel S. Evans, Hans-Jörgen Grabe, Yongmei Liu, Danyu Lin, Albert Hofman, George McMahon, Naomi R. Wray, Stefan Herms, Stefania Bandinelli, W. Hoffmann, P.F. Sullivan, Susanne Hoefels, Michael B. Miller, Alan W. McLean, Igor Rudan, Jürgen Wellmann, Anu Realo, Maurizio Fava, Matthew Kowgier, Marika Kaakinen, Helena Schmidt, Faculteit Medische Wetenschappen/UMCG, Peyrot, WJ, Lee, SH, Milaneschi, Y, Abdellaoui, A, Penninx, BWJH, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium, Social Science Genetic Association Consortium, Psychiatry, NCA - Neurobiology of mental health, EMGO - Mental health, Applied Economics, Biological Psychology, Complex Trait Genetics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Mental Health, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium (Corporate Collaborator), Social Science Genetic Association Consortium Corporate Collaborator, Major Depressive Disorder Working Group of the Psychiatric GWAS Consortium Corporate Collaborator, Lewis, C.M., Hamilton, S.P., Weissman, M.M., Breen, G., Blackwood, D.H., Cichon, S., Heath, A.C., Holsboer, F., Madden, P.A., McGuffin, P., Muglia, P., Pergadia, M.L., Lin, D., Müller-Myhsok, B., Steinberg, S., Grabe, H.J., Lichtenstein, P., Magnusson, P., Perlis, R.H., Preisig, M., Smoller, J.W., Stefansson, K., Uher, R., Kutalik, Z., Tansey, K.E., Teumer, A., Viktorin, A., Barnes, M.R., Bettecken, T., Binder, E.B., Breuer, R., Castro, V.M., Churchill, S.E., Coryell, W.H., Craddock, N., Craig, I.W., Czamara, D., Degenhardt, F., Farmer, A.E., Fava, M., Frank, J., Gainer, V.S., Gallagher, P.J., Gordon, S.D., Goryachev, S., Gross, M., Guipponi, M., Henders, A.K., Herms, S., Hickie, I.B., Hoefels, S., Hoogendijk, W., Iosifescu, D.V., Ising, M., Jones, I., Jones, L., Jung-Ying, T., Knowles, J.A., Kohane, I.S., Kohli, M.A., Korszun, A., Landen, M., Lawson, W.B., Lewis, G., Macintyre, D., Maier, W., Mattheisen, M., McGrath, P.J., McIntosh, A., McLean, A., Middeldorp, C.M., Middleton, L., Montgomery, G.M., Murphy, S.N., Nauck, M., Nolen, W.A., Nyholt, D.R., O'Donovan, M., Oskarsson, H., Pedersen, N., Scheftner, W.A., Schulz, A., Schulze, T.G., Shyn, S.I., Sigurdsson, E., Slager, S.L., Smit, J.H., Stefansson, H., Steffens, M., Thorgeirsson, T., Tozzi, F., Treutlein, J., Uhr, M., van den Oord, E.J., Van Grootheest, G., Völzke, H., Weilburg, J.B., Willemsen, G., Zitman, F.G., Neale, B., Daly, M., Sullivan, P.F., Agrawal, A., Albrecht, E., Alizadeh, B.Z., Allik, J., Amin, N., Attia, J.R., Bandinelli, S., Barnard, J., Bastardot, F., Baumeister, S.E., Beauchamp, J., Benjamin, D.J., Benke, K.S., Bennett, D.A., Berger, K., Bielak, L.F., Bierut, L.J., Boatman, J.A., Boyle, P.A., Bültmann, U., Campbell, H., Cesarini, D., Chabris, C.F., Cherkas, L., Chung, M.K., Conley, D., Cucca, F., Davey-Smith, G., Davies, G., de Andrade, M., De Jager, P.L., de Leeuw, C., De Neve, J.E., Deary, I.J., Dedoussis, G.V., Deloukas, P., Derringer, J., Dimitriou, M., Eiriksdottir, G., Eklund, N., Elderson, M.F., Eriksson, J.G., Evans, D.S., Evans, D.M., Faul, J.D., Fehrmann, R., Ferrucci, L., Fischer, K., Franke, L., Garcia, M.E., Gieger, C., Gjessing, H.K., Groenen, P.J., Grönberg, H., Gudnason, V., Hägg, S., Hall, P., Harris, J.R., Harris, J.M., Harris, T.B., Hastie, N.D., Hayward, C., Hernandez, D.G., Hoffmann, W., Hofman, A., Holle, R., Holliday, E.G., Holzapfel, C., Iacono, W.G., Ibrahim-Verbaas, C.A., Illig, T., Ingelsson, E., Jacobsson, B., Järvelin, M.R., Jhun, M.A., Johannesson, M., Joshi, P.K., Jugessur, A., Kaakinen, M., Kähönen, M., Kanoni, S., Kaprio, J., Kardia, S.L., Karjalainen, J., Kirkpatrick, R.M., Koellinger, P.D., Kolcic, I., Kowgier, M., Kristiansson, K., Krueger, R.F., Lahti, J., Laibson, D., Latvala, A., Launer, L.J., Lawlor, D.A., Lethimäki, T., Li, J., Lichtner, P.K., Liewald, D.C., Lin, P., Lind, P.A., Liu, Y., Lohman, K., Loitfelder, M., Magnusson, P.K., Mäkinen, T.E., Vidal, P.M., Martin, N.W., Masala, M., McGue, M., McMahon, G., Meirelles, O., Meyer, M.N., Mielck, A., Milani, L., Miller, M.B., Montgomery, G.W., Mukherjee, S., Myhre, R., Nuotio, M.L., Oldmeadow, C.J., Oostra, B.A., Palmer, L.J., Palotie, A., Perola, M., Petrovic, K.E., Peyser, P.A., Polašek, O., Posthuma, D., Quaye, L., Räikkönen, K., Raitakari, O.T., Realo, A., Reinmaa, E., Rice, J.P., Ring, S.M., Ripatti, S., Rivadeneira, F., Rizzi, T.S., Rudan, I., Rustichini, A., Salomaa, V., Sarin, A.P., Schlessinger, D., Schmidt, H., Schmidt, R., Scott, R.J., Shakhbazov, K., Smith, A.V., Smith, J.A., Snieder, H., Pourcain, B.S., Starr, J.M., Sul, J.H., Surakka, I., Svento, R., Tanaka, T., Terracciano, A., Thurik, A.R., Tiemeier, H., Timpson, N.J., Uitterlinden, A.G., van der Loos, M.J., van Duijn, C.M., van Rooij, F.J., Van Wagoner, D.R., Vartiainen, E., Viikari, J., Visscher, P.M., Vitart, V., Vollenweider, P.K., Vonk, J.M., Waeber, G., Weir, D.R., Wellmann, J., Westra, H.J., Wichmann, H.E., Widen, E., Wilson, J.F., Wright, A.F., Yang, J., Yu, L., and Zhao, W.
Subjects: Netherlands Twin Register (NTR), Male, Genome-wide association study, Logistic regression, Cohort Studies, Odds Ratio, pleiotropic genetic effects, Netherlands, Psychiatry, education.field_of_study, Likelihood Functions, Single Nucleotide, Middle Aged, Psychiatry and Mental health, educational attainment, depression, Major depressive disorder, Educational Status, Regression Analysis, Female, Psychology, Adult, Estonia, medicine.medical_specialty, Biochemistry & Molecular Biology, Aged, Depressive Disorder, Major/epidemiology, Depressive Disorder, Major/genetics, Depressive Disorder, Major/psychology, Estonia/epidemiology, Gene-Environment Interaction, Genetic Association Studies, Genotype, Humans, Netherlands/epidemiology, Polymorphism, Single Nucleotide/genetics, Psychiatric Status Rating Scales, Concordance, Population, SNP, Single-nucleotide polymorphism, Genetic correlation, behavioral disciplines and activities, Polymorphism, Single Nucleotide, Article, Cellular and Molecular Neuroscience, mental disorders, medicine, Polymorphism, education, Molecular Biology, Depressive Disorder, Depressive Disorder, Major, major depressive disorder, ta1184, Neurosciences, Major, Odds ratio, medicine.disease, ta3124, Neurosciences & Neurology, polymorphisms, Demography
Abstract: An association between lower educational attainment (EA) and an increased risk for depression has been confirmed in various western countries. This study examines whether pleiotropic genetic effects contribute to this association. Therefore, data were analyzed from a total of 9662 major depressive disorder (MDD) cases and 14 949 controls (with no lifetime MDD diagnosis) from the Psychiatric Genomics Consortium with additional Dutch and Estonian data. The association of EA and MDD was assessed with logistic regression in 15 138 individuals indicating a significantly negative association in our sample with an odds ratio for MDD 0.78 (0.75-0.82) per standard deviation increase in EA. With data of 884 105 autosomal common single-nucleotide polymorphisms (SNPs), three methods were applied to test for pleiotropy between MDD and EA: (i) genetic profile risk scores (GPRS) derived from training data for EA (independent meta-analysis on similar to 120 000 subjects) and MDD (using a 10-fold leave-one-out procedure in the current sample), (ii) bivariate genomic-relationship-matrix restricted maximum likelihood (GREML) and (iii) SNP effect concordance analysis (SECA). With these methods, we found (i) that the EA-GPRS did not predict MDD status, and MDD-GPRS did not predict EA, (ii) a weak negative genetic correlation with bivariate GREML analyses, but this correlation was not consistently significant, (iii) no evidence for concordance of MDD and EA SNP effects with SECA analysis. To conclude, our study confirms an association of lower EA and MDD risk, but this association was not because of measurable pleiotropic genetic effects, which suggests that environmental factors could be involved, for example, socioeconomic status. Refereed/Peer-reviewed
Published: 2015

42. Is there an influence of X-chromosomal imprinting on the phenotype in Klinefelter syndrome? A clinical and molecular genetic study of 61 cases

Author: T Roza, Jacques C. Giltay, D Stemkens, Behrooz Z. Alizadeh, M K van Werkhoven, Richard J. Sinke, L Verrij, and Hanna Swaab
Subjects: Genetics, Psychomotor learning, medicine.medical_specialty, Autosome, Aneuploidy, Biology, medicine.disease, Endocrinology, Internal medicine, Turner syndrome, medicine, Imprinting (psychology), Klinefelter syndrome, Genomic imprinting, Genetics (clinical), X chromosome
Abstract: Studies on Turner syndrome suggested the presence of X-chromosomal-imprinted genes involved in social and verbal cognition. Imprinted genes on autosomes were shown to affect growth. Could imprinting of such genes on the X chromosome also influence psychomotor development and growth in men with Klinefelter syndrome (KS), who have a supernumerary X? We recorded anthropometric and psychomotor development parameters for 61 males with KS (age range 2-56 years). In 54 cases, we were able to assess intelligence quotient (IQ) and found that impaired speech - and motor developmental problems were reported significantly more often in the paternal X - than in the maternal X group (P = 0.02). We found some significant (P < 0.05) increased body size parameters in the paternal X group, which concurs with data reporting a growth promoting influence of paternally derived genes. Our results suggest X-chromosomal imprinting occurs in males with KS.
Published: 2006

43. Premorbid Adjustment Profiles in Psychosis and the Role of Familial Factors

Author: Edwin R. van den Heuvel, Grp Investigators, Carin J. Meijer, Piotr J. Quee, Atiqul Islam, André Aleman, Behrooz Z. Alizadeh, Julia H. Meijer, Clinical Neuropsychology, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Perceptual and Cognitive Neuroscience (PCN), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Amsterdam Neuroscience, Adult Psychiatry, and Other departments
Subjects: Adult, Male, Psychosis, medicine.medical_specialty, SYMPTOMS, SAMPLE, Early adolescence, FEATURES, Disease, Young Adult, Cognition, Adaptation, Psychological, medicine, Humans, developmental, In patient, Psychiatry, Biological Psychiatry, Psychiatric Status Rating Scales, RISK, Middle Aged, PERFORMANCE, Late adolescence, medicine.disease, schizophrenia, Clinical Psychology, Psychiatry and Mental health, Psychotic Disorders, Schizophrenia, premorbid, RELIABILITY, Etiology, PATTERNS, Female, heterogeneity, Psychology, Social Adjustment, FORM, Clinical psychology, cluster analysis
Abstract: Disease heterogeneity in patients with psychotic disorder may be explained by distinct profiles of premorbid adjustment. The current study explored premorbid adjustment profiles in patients with psychotic disorders, associations with cognitive and clinical characteristics after disease onset, and the role of familial factors. A total of 666 patients with psychosis (predominantly schizophrenia), 673 siblings, 575 parents, and 585 controls were included in this study. Cluster analyses were performed on the patients' scores of the Premorbid Adjustment Scale (PAS), using information on domains (social, academic) and age epochs (childhood, early adolescence, late adolescence). Resulting profiles were compared with characteristics in patients and their unaffected relatives. Six clusters, labeled normal, social intermediate, academic decline, overall decline, overall intermediate, and overall impaired adjustment, were identified in patients. Patients in different clusters differed from each other on cognitive, clinical, and functional characteristics after disease onset. Heterogeneity in the patient population may be explained in part by the adjustment profile prior to disease onset. This is in line with theories that propose different etiologies in the development of psychosis. Patient profiles were expressed in unaffected siblings, suggesting a role for familial factors.
Published: 2014

44. Clarithromycin vs. furazolidone in quadruple therapy regimens for the treatment ofHelicobacterpylori in a population with a high metronidazole resistance rate

Author: Morteza Khatibian, Ali Fazel, Reza Malekzadeh, Behrooz Z. Alizadeh, Sadegh Massarrat, H. Fakheri, and Shahin Merat
Subjects: education.field_of_study, medicine.medical_specialty, Hepatology, biology, business.industry, Population, Gastroenterology, Drug resistance, Helicobacter pylori, bacterial infections and mycoses, biology.organism_classification, Surgery, Metronidazole, Bismuth Subcitrate, Clarithromycin, Internal medicine, medicine, Pharmacology (medical), education, business, Omeprazole, medicine.drug, Antibacterial agent
Abstract: Background: The eradication of Helicobacter pylori plays a pivotal role in the treatment of peptic ulcer disease. Metronidazole resistance, common in Iran, is claimed to be a major reason for the failure of metronidazole-containing regimens. Both clarithromycin and furazolidone are potential alternatives for metronidazole. Aim: To assess and compare the effectiveness of clarithromycin- and furazolidone-based regimens in eradicating H. pylori in a population with a high metronidazole resistance rate. Methods: Patients with proven duodenal ulcer and H. pylori infection were randomly assigned to one of two groups. The patients received 2 weeks of omeprazole 20 mg b.d., amoxicillin 1000 mg b.d, bismuth subcitrate 240 mg b.d. and either clarithromycin 500 mg b.d. (the OABC group) or furazolidone 200 mg b.d. (the OABF group). Results: A total of 118 patients were randomized, 55 in the OABC group and 63 in the OABF group. The intention-to-treat eradication rate was 84% and 85% for the OABF and OABC groups, respectively. The per protocol eradication rates were 90% for both groups. Conclusions: OABC and OABF are both effective in eradicating H. pylori in areas where metronidazole resistance is a problem. OABF is a good alternative in the face of growing resistance to clarithromycin in developed countries, and is attractive for developing countries where clarithromycin is not readily available.
Published: 2001

45. Correction: Corrigendum: Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses

Author: Nicholas A. Furlotte, S. Fleur W. Meddens, Ronald de Vlaming, Anu Realo, Bart M. L. Baselmans, Patrick Turley, Jacob Gratten, Jan-Emmanuel De Neve, Melinda Mills, Alexis C. Frazier-Wood, Marie Henrike Geisel, Peter J. van der Most, Richard Karlsson Linnér, Saskia Haitjema, Tian Liu, Yong Qian, Juan R. González, Ilja M. Nolte, Sven J. van der Lee, Harm-Jan Westra, Jaime Derringer, Mark Alan Fontana, Behrooz Z. Alizadeh, Jimmy Z. Liu, Meena Kumari, Evelin Mihailov, Tarunveer S. Ahluwalia, Jadwiga Buchwald, Alana Cavadino, Penelope A. Lind, Aysu Okbay, Christopher Oldmeadow, Harold Snieder, Michael B. Miller, Albertine J. Oldehinkel, Sander W. van der Laan, Camelia C. Minică, Michel G. Nivard, Dennis O. Mook-Kanamori, Victoria Garfield, Karl-Heinz Ladwig, Lindsay K. Matteson, James J. Lee, Ute Bültmann, Olli T. Raitakari, Robert Karlsson, Lude Franke, Rajesh Rawal, Cornelius A. Rietveld, and Jari Lahti
Subjects: 0301 basic medicine, medicine.medical_specialty, Public health, Genetic variants, Biology, Neuroticism, Genome, 03 medical and health sciences, 030104 developmental biology, Genetics, medicine, Subjective well-being, Depressive symptoms, Clinical psychology
Abstract: In the version of this article initially published, one of the affiliations listed for author Maciej Trzaskowski, to the Department of Public Health, Faculty of Medicine, University of Split, Split, Croatia, was included in error. The correct affiliation for this author is the Queensland Brain Institute, University of Queensland, Brisbane, Queensland, Australia. The error has been corrected in the HTML and PDF versions of the article.
Published: 2016

46. Association of the CLCA1 p.S357N Variant With Meconium Ileus in European Patients With Cystic Fibrosis

Author: M. G. Slieker, Carla Colombo, Roderick H. J. Houwen, D. Staab, Behrooz Z. Alizadeh, C. K. van der Ent, H. P. J. van der Doef, Manuela Seia, Renate Nickel, and Heiko Witt
Subjects: Adult, Male, Meconium, congenital, hereditary, and neonatal diseases and abnormalities, Pathology, medicine.medical_specialty, Pancreatic disease, Adolescent, Cystic Fibrosis, Genotype, Ileus, Cystic Fibrosis Transmembrane Conductance Regulator, Meconium Ileus, Cystic fibrosis, Young Adult, Chloride Channels, medicine, Humans, Intestine obstruction, Child, biology, business.industry, Respiratory disease, Infant, Newborn, Gastroenterology, Genetic Variation, respiratory system, medicine.disease, digestive system diseases, Cystic fibrosis transmembrane conductance regulator, Europe, Pediatrics, Perinatology and Child Health, biology.protein, Female, business
Abstract: In Cftr-/- mice that mostly die because of intestinal obstruction, intestinal expression of Clca3 is decreased, whereas upregulation of Clca3 results in amelioration of intestinal disease. The aim of the study was to investigate whether the p.S357N variant in CLCA1, the human orthologue of Clca3, acts as a modifier gene in a cohort of 682 European patients with cystic fibrosis (CF)-99 patients with meconium ileus. The 357SS genotype was significantly overrepresented in both patients with meconium ileus and also with a severe CFTR genotype (P = 0.009) and in p.F508del homozygotes (P = 0.002). This suggests that CLCA1 has similar important functions in CF-related intestinal obstruction in humans as in Cftr-/- mice.
Published: 2010

47. Furazolidone versus metronidazole in quadruple therapy for eradication of Helicobacter pylori in duodenal ulcer disease

Author: Mohammad Reza Eshraghian, Behrooz Z. Alizadeh, Sadegh Massarrat, Mohsen Saghari, H Vahedi, Reza Ansari, Reza Malekzadeh, Farideh Siavoshi, and Arsalan Vakili
Subjects: medicine.medical_specialty, Hepatology, Furazolidone, biology, business.industry, Gastroenterology, Rapid urease test, Amoxicillin, Helicobacter pylori, biology.organism_classification, Surgery, Ranitidine, Metronidazole, Bismuth Subcitrate, Internal medicine, medicine, Pharmacology (medical), business, medicine.drug, Antibacterial agent
Abstract: OBJECTIVE: Furazolidone, an old but cheap antibiotic, was shown to be a good alternative to metronidazole in triple therapy for Helicobacter pylori eradication in areas where metronidazole resistant bacteria are common, but randomized studies are lacking. AIM: A randomized controlled trial to determine the efficacy and safety of furazolidone compared to metronidazole in classic quadruple therapy for eradication of H. pylori infection in duodenal ulcer patients. METHODS: Patients with endoscopically proven duodenal ulcer and positive urease test were randomized to receive ranitidine 300 mg, amoxycillin 1000 mg and bismuth subcitrate 240 mg b.d, with either furazolidone 200 mg b.d (RABF), or metronidazole 500 mg b.d. (RABM) for 2 weeks. Compliance and side-effects were monitored and recorded by table diary. H. pylori eradication was assessed at least 4 weeks after the completion of therapy with 14C-urea breath test. RESULTS: A total of 106 patients were enrolled and 101 (59 male, 42 female, mean age=40 +/- 11 years) completed the study. Endoscopic findings and demographic data were comparable in both groups. Intention-to-treat eradication rates were 75% and 55% (P=0.03) and per protocol eradication rates were 82 and 56% (P=0. 006) in the RABF and RABM groups, respectively. Side-effects were reported by 13 patients (27%) in the RABF group (one stopped treatment) compared to five patients (10%) in the RABM group (P=0. 04). CONCLUSION: Quadruple therapy containing furazolidone, instead of metronidazole, results in a significantly higher H. pylori eradication rate in Iranian duodenal ulcer patients.
Published: 2000

48. Serum Ghrelin; A New Surrogate Marker of Gastric Mucosal Alterations in Upper Gastrointestinal Carcinogenesis

Author: Behrooz Z. Alizadeh, Alireza Sadjadi, Masoud Sotoudeh, Geertruida H. de Bock, Mohammad H. Derakhshan, Fatemeh Samadi, James J. Going, Farhad Islami, Abbas Yazdanbod, Valerie Fyfe, Yeong Yeh Lee, Reza Malekzadeh, Mohammad Javad Namazi, Masoud Babaei, Majid Boreiri, Damage and Repair in Cancer Development and Cancer Treatment (DARE), Life Course Epidemiology (LCE), and Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI)
Subjects: Esophageal Neoplasms, Atrophic gastritis, ESOPHAGEAL CANCER, lcsh:Medicine, Gastroenterology, Pepsinogen A, Odds Ratio, Pepsinogen C, INCREASED RISK-FACTOR, lcsh:Science, education.field_of_study, Multidisciplinary, CARDIA CANCER, digestive, oral, and skin physiology, Esophageal cancer, Ghrelin, medicine.anatomical_structure, Adenocarcinoma, SQUAMOUS-CELL CARCINOMA, Gastritis, medicine.symptom, 2 DISTINCT ETIOLOGIES, Research Article, medicine.medical_specialty, Population, Statistics, Nonparametric, ATROPHY, Stomach Neoplasms, Internal medicine, medicine, Gastric mucosa, Biomarkers, Tumor, Humans, education, JAPAN, business.industry, lcsh:R, Cancer, ADENOCARCINOMA, medicine.disease, digestive system diseases, HELICOBACTER-PYLORI INFECTION, Endocrinology, Logistic Models, SEROLOGICAL MARKERS, Gastric Mucosa, Immunoglobulin G, lcsh:Q, business
Abstract: Background: A few studies have indicated inverse relationships between serum ghrelin and gastric and esophageal cancers but those associations have been restricted to specific populations, including smokers and overweight individuals. We examined the association between ghrelin and gastroesophageal cancers and atrophic gastritis in a population-based setting.Methods: In total 220 gastroesophageal cancers, comprising non-cardia and cardia gastric cancer, esophageal adenocarcinoma, esophageal squamous cell carcinoma (SCC) and age and gender-matched controls were recruited. Serum ghrelin, pepsinogen I/II ratio (PGI/II) and anti-H. pylori IgG antibodies were measured. Relationships between ghrelin and gastroesophageal cancers, after adjustment for PGI/II ratio, H. pylori status and smoking, were tested using logistic regression. Furthermore, in 125 endoscopically normal volunteers, with and without histological atrophic gastritis, the relationship with ghrelin was compared.Results: Serum ghrelin (lowest vs. highest quintile) was inversely associated with gastric cancer: OR (95% CI) 8.71 (1.70-44.59) for cardia and 6.58 (1.26-34.46) for non-cardia cancer. Lower serum ghrelin was also associated with esophageal SCC: OR (95% CI) 5.69 (1.36-23.78), but not with esophageal adenocarcinoma. A similar association was observed between gastric cancer (cardia and non-cardia) and esophageal SCC when serum ghrelin was analysed as a continuous scaled variable. In endoscopically-normal volunteers, extensive atrophic gastritis was associated with low serum ghrelin [OR (95% CI) 0.25 (0.10-0.64)].Conclusion: Inverse associations between ghrelin and some gastroesophageal cancers suggest a potential role for serum ghrelin as a biomarker of upper gastrointestinal cancers and atrophic gastritis. In areas with a high incidence of gastric and/or esophageal cancer, screening might be more effectively targeted to individuals with low serum ghrelin in addition to the PGI/II ratio.
Published: 2013

49. GWAS of 126559 Individuals Identifies Genetic Variants Associated with Educational Attainment

Author: Maria Dimitriou, Klaus Berger, Jian Yang, Nicholas J. Timpson, George Dedoussis, Magnus Johannesson, Igor Rudan, Marisa Loitfelder, Kurt Lohman, Jürgen Wellmann, Osorio Meirelles, Johan G. Eriksson, Cornelia M. van Duijn, Francesco Cucca, Anu Realo, Gérard Waeber, David R. Van Wagoner, Samuli Ripatti, Alan F. Wright, George McMahon, Elizabeth G. Holliday, Lili Milani, Ute Bültmann, Olli T. Raitakari, Behrooz Z. Alizadeh, Reinhold Schmidt, Matthew Kowgier, André G. Uitterlinden, Sutapa Mukherjee, William G. Iacono, Judith M. Vonk, Lude Franke, John M. Starr, Antonio Terracciano, Rudolf Ferhmann, Pamela A. F. Madden, Marika Kaakinen, Helena Schmidt, Dorret I. Boomsma, Harry Campbell, Konstantin Shakhbazov, Lei Yu, Albert Hofman, Tõnu Esko, Cornelius A. Rietveld, Albert V. Smith, Arpana Agrawal, Wouter J. Peyrot, Stefania Bandinelli, David M. Evans, Nicolas W. Martin, Martin F. Elderson, Melissa E. Garcia, Danielle Posthuma, Ozren Polasek, Panos Deloukas, Pedro Marques Vidal, Sang Hong Lee, James F. Wilson, Robert F. Krueger, Paul Lichtenstein, Jan-Emmanuel De Neve, Fernando Rivadeneira, Laura J. Bierut, Sebastian E. Baumeister, Lawrence F. Bielak, Peter M. Visscher, Philipp Koellinger, Thais S. Rizzi, Rodney J. Scott, Mika Kähönen, Marco Masala, Debbie A Lawlor, Yongmei Liu, Ben A. Oostra, Jaime Derringer, Zoltán Kutalik, Carla A. Ibrahim-Verbaas, Toshiko Tanaka, Håkon K. Gjessing, Jae Hoon Sul, Marjo-Riitta Järvelin, Krista Fischer, Erik Ingelsson, David R. Weir, Kati Kristiansson, Thomas Illig, Jorma Viikari, George Davey-Smith, Antti-Pekka Sarin, Matt McGue, Ida Surakka, Andreas Mielck, Ivana Kolcic, Astanand Jugessur, Aldo Rustichini, Sarah E. Medland, Ronny Myhre, Veikko Salomaa, Mina K. Chung, H.-Erich Wichmann, Lynn Cherkas, Peter Lichtner, Michael B. Miller, Peter Vollenweider, Jüri Allik, Henning Tiemeier, Grant W. Montgomery, Eva Reinmaa, Dalton Conley, Adriaan Hofman, Patricia A. Peyser, David Schlessinger, Martin Preisig, Jessica D. Faul, Patrik K. E. Magnusson, David A. Bennett, Erkki Vartiainen, David Laibson, François Bastardot, Niina Eklund, Wolfgang Hoffmann, Terho Lehtimäki, Nicholas D. Hastie, John P. Rice, Rolf Holle, Antti Latvala, Guoný Eiríksdóttir, Luigi Ferrucci, Jennifer A. Smith, Christian Gieger, Veronique Vitart, Gail Davies, Sara Hägg, Juha Karjalainen, Matthijs J. H. M. van der Loos, Bo Jacobsson, Lydia Quaye, John Barnard, Beate St Pourcain, Jouke-Jan Hottenga, Daniel S. Evans, Jonathan P. Beauchamp, Tamara B. Harris, Ian J. Deary, Jari Lahti, Peng Lin, Markus Perola, Henry Völzke, Lenore J. Launer, David C. Liewald, Brenda W.J.H. Penninx, David Cesarini, Najaf Amin, Dale R. Nyholt, Roy Thurik, Aarno Palotie, Patrick J. F. Groenen, Elisabeth Widen, Caroline Hayward, Penelope A. Lind, Susan M. Ring, Lyle J. Palmer, Alexander Teumer, Kelly S. Benke, Christopher Oldmeadow, Katja Petrovic, Gonneke Willemsen, Andrew C. Heath, Harold Snieder, Jaakko Kaprio, Marja-Liisa Nuotio, Frank J. A. van Rooij, Robert M. Kirkpatrick, Nicholas G. Martin, Tomi E. Mäkinen, Michelle N. Meyer, Katri Räikkönen, Harm-Jan Westra, Daniel J. Benjamin, Jeffrey A. Boatman, Henrik Grönberg, Eva Albrecht, Sharon L.R. Kardia, Peter K. Joshi, Philip L. De Jager, Mariza de Andrade, Patricia A. Boyle, Jennifer R. Harris, Vilmundur Guonason, Christiaan de Leeuw, Juliette Harris, Dena G. Hernandez, Jingmei Li, Per Hall, Wei Zhao, Abdel Abdellaoui, Andres Metspalu, Christina Holzapfel, Stavroula Kanoni, Christopher F. Chabris, John Attia, Rauli Svento, Erasmus School of Economics, Epidemiology, Surgery, Neurology, Applied Economics, Research Methods and Techniques, Clinical Genetics, Internal Medicine, Child and Adolescent Psychiatry / Psychology, Econometrics, Neuroscience Campus Amsterdam - Neurobiology of Mental Health, EMGO+ - Lifestyle, Overweight and Diabetes, Neuroscience Campus Amsterdam - Brain Mechanisms in Health & Disease, Biological Psychology, Functional Genomics, Management and Organisation, Tinbergen Institute, Amsterdam Neuroscience - Complex Trait Genetics, Rietveld, Cornelius A, Medland, Sarah E, Derringer, Jaime, Yang, Jian, Lee, Sang Hong, Koellinger, Philipp D, LifeLines Cohort Study, ABS Other Research (FEB), Reproductive Origins of Adult Health and Disease (ROAHD), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Life Course Epidemiology (LCE), Damage and Repair in Cancer Development and Cancer Treatment (DARE), Guided Treatment in Optimal Selected Cancer Patients (GUTS), Public Health Research (PHR), Teaching and Teacher Education, Groningen Research Institute for Asthma and COPD (GRIAC), Stem Cell Aging Leukemia and Lymphoma (SALL), Psychiatry, Human genetics, NCA - Brain mechanisms in health and disease, NCA - Neurobiology of mental health, and EMGO - Lifestyle, overweight and diabetes
Subjects: Netherlands Twin Register (NTR), Male, medicine.medical_specialty, Multifactorial Inheritance, Endophenotypes, social-science genetics, LOCI, SNP, Single-nucleotide polymorphism, Genome-wide association study, Biology, PREFERENCES, Polymorphism, Single Nucleotide, 03 medical and health sciences, 0302 clinical medicine, Cognition, Polymorphism (computer science), medicine, GWAS, Humans, Allele, Polymorphism, education, gene, attainment, 030304 developmental biology, Genetics, 0303 health sciences, ENVIRONMENT, genome-wide association study, Multidisciplinary, Data Science, Replicate, Single Nucleotide, single-nucleotide polymorphism, linear polygenic score, ta3121, Educational attainment, Multidisciplinary Sciences, Educational Status, Female, Genetic Loci, Genome-Wide Association Study, educational attainment, Endophenotype, Medical genetics, 030217 neurology & neurosurgery
Abstract: Genetic College Many genomic elements in humans are associated with behavior, including educational attainment. In a genome-wide association study including more than 100,000 samples, Rietveld et al. (p. 1467 , published online 30 May; see the Perspective by Flint and Munafò ) looked for genes related to educational attainment in Caucasians. Small genetic effects at three loci appeared to impact educational attainment.
Published: 2013

50. Clinical response to antipsychotic drug treatment: Association study of polymorphisms in six candidate genes

Author: A. F. Y. Al Hadithy, Bob Wilffert, Harold Snieder, Behrooz Z. Alizadeh, Huibert Burger, Jelle Vehof, Science in Healthy Ageing & healthcaRE (SHARE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Methods in Medicines evaluation & Outcomes research (M2O), Reproductive Origins of Adult Health and Disease (ROAHD), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Psychiatrie & Neuropsychologie, RS: MHeNs School for Mental Health and Neuroscience, ANS - Amsterdam Neuroscience, Adult Psychiatry, Medical Oncology, Pharmacy, and Epidemiology
Subjects: Male, Oncology, Candidate gene, PROMOTER, Dopamine, Pharmacology, chemistry.chemical_compound, 1ST-EPISODE SCHIZOPHRENIA, Antipsychotics, Pharmacology (medical), Longitudinal Studies, biology, Response, Middle Aged, Psychiatry and Mental health, Phenotype, Neurology, Schizophrenia, Female, ALLELIC VARIATION, Psychology, Antipsychotic Agents, medicine.drug, Adult, medicine.medical_specialty, Serotonin, DOPAMINE D-3 RECEPTOR, Adolescent, Genotype, TaqI, Clinical Neurology, Single-nucleotide polymorphism, SCHIZOPHRENIA-PATIENTS, Polymorphism, Single Nucleotide, White People, METHYLENETETRAHYDROFOLATE REDUCTASE, Internal medicine, medicine, Humans, Polymorphism, Genetic Association Studies, Methylenetetrahydrofolate Reductase (NADPH2), Biological Psychiatry, Psychiatric Status Rating Scales, CLOZAPINE RESPONSE, Risperidone, Receptors, Dopamine D3, medicine.disease, 5-HT2A RECEPTOR, Psychotic Disorders, chemistry, Pharmacogenetics, Methylenetetrahydrofolate reductase, A1 ALLELE, biology.protein, Clinical Global Impression, Neurology (clinical), HEALTHY-VOLUNTEERS
Abstract: Pharmacogenetic studies have demonstrated significant associations between several candidate genes (DRD2, DRD3, 5HTR2A and 5HTR2C, COMT and MTHFR) and antipsychotic drug response. The present study investigates the effect of nine polymorphisms in these genes for an association with antipsychotic treatment response. 329 Caucasian patients with a non-affective psychotic disorder using antipsychotics were included. All patients participated in the longitudinal GROUP-study in The Netherlands. We genotyped 9 SNPs in 6 candidate genes (DRD2: Taql_A, -141C; DRD3: Ser9Gly; HTR2A: 102-T/C, His452Tyr; HTR2C: Cys23Ser; COMT: Val158Met; MTHFR: 677-C/T) using standard protocols. Polymorphisms were based on previous studies showing associations with positive symptoms treatment response. The Clinical Global Impression Improvement (CGI-I) scale was used to assess improvement in positive psychotic symptoms since the start of current antipsychotic treatment. Ordinal regression was used for association analyses. Ninety percent of the patients used second generation antipsychotics, with olanzapine (28%) and risperidone (29%) being the most prescribed drugs. Ser9Gly of the dopamine D3 receptor gene (P value 0.034) and 677-C/T of MTHFR (P value 0.019) were tested statistically significant. Gly-carriers and T-carriers, respectively, showed more clinical improvement on the CGI-I. The other polymorphisms did not show a statistically significant association (P values>0.10). In conclusion, we replicated two out of nine of the previously reported associations between polymorphisms and treatment response. The direction and magnitude of the associations presented here in DRD3 (Ser9Gly) and MTHFR (677-C/T) are in line with previous association studies in Caucasian patients. These polymorphisms may be of value for predicting clinical response. (C) 2012 Elsevier B.V. and ECNP. All rights reserved.
Published: 2012

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