10 results on '"Miao-Ling Chee"'
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2. Common variants in SOX-2 and congenital cataract genes contribute to age-related nuclear cataract
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Preeti Gupta, Maryam Hazly Hilmy, Jie Jin Wang, Jiemin Liao, Allan Fong, Maria K. Swift, Johanna M. Colijn, Paul Mitchell, Ya Xing Wang, Anita S Y Chan, Barbara E.K. Klein, Pirro G. Hysi, Jaeyoon Chung, Emily Y. Chew, Wanting Zhao, Yang Shen, Ava Grace Tan, Hengtong Li, Eranga N. Vithana, Gyungah Jun, Wenting Liu, Tin Aung, Qiao Fan, Yuan Shi, Ekaterina Yonova-Doing, Soon-Phaik Chee, Sudha K. Iyengar, Yik Ying Teo, Periasamy Sundaresan, Chiea Chuen Khor, Zheng Li, Kathryn P. Burdon, Miao Ling Chee, Yih Chung Tham, Christopher J Hammond, Xiaoran Chai, Kerrin S. Small, Queenie S. Tan, Jacqueline Chua, Jost B. Jonas, Astrid E. Fletcher, Alexessander Couto Alves, Pieter W.M. Bonnemaijer, Ravilla D. Ravindran, Mei Chin Lee, Milly S. Tedja, Robert P. Igo, Kristine E. Lee, Tien Y Wong, Xinyi Su, Caroline C W Klaver, Xueling Sim, Ching-Yu Cheng, Chaolong Wang, Lars G. Fritsche, Epidemiology, and Ophthalmology
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0301 basic medicine ,Genotype ,genetic structures ,QH301-705.5 ,Medicine (miscellaneous) ,Genome-wide association study ,Disease ,Bioinformatics ,Polymorphism, Single Nucleotide ,Genome-wide association studies ,Cataract ,Article ,Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12] ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,All institutes and research themes of the Radboud University Medical Center ,0302 clinical medicine ,Genetic variation ,Humans ,Medicine ,Genetic Predisposition to Disease ,Allele ,Biology (General) ,Alleles ,Genetic Association Studies ,Genetic association ,business.industry ,SOXB1 Transcription Factors ,Genetic Variation ,medicine.disease ,eye diseases ,030104 developmental biology ,Age-related nuclear cataract ,030221 ophthalmology & optometry ,Congenital cataracts ,Lens diseases ,sense organs ,General Agricultural and Biological Sciences ,business ,Genome-Wide Association Study - Abstract
Nuclear cataract is the most common type of age-related cataract and a leading cause of blindness worldwide. Age-related nuclear cataract is heritable (h2 = 0.48), but little is known about specific genetic factors underlying this condition. Here we report findings from the largest to date multi-ethnic meta-analysis of genome-wide association studies (discovery cohort N = 14,151 and replication N = 5299) of the International Cataract Genetics Consortium. We confirmed the known genetic association of CRYAA (rs7278468, P = 2.8 × 10−16) with nuclear cataract and identified five new loci associated with this disease: SOX2-OT (rs9842371, P = 1.7 × 10−19), TMPRSS5 (rs4936279, P = 2.5 × 10−10), LINC01412 (rs16823886, P = 1.3 × 10−9), GLTSCR1 (rs1005911, P = 9.8 × 10−9), and COMMD1 (rs62149908, P = 1.2 × 10−8). The results suggest a strong link of age-related nuclear cataract with congenital cataract and eye development genes, and the importance of common genetic variants in maintaining crystalline lens integrity in the aging eye., Here, the authors report a multi-ethnic genome wide association meta-analysis of 12 studies from the International Cataract Genetics Consortium. They find six new loci associated with age-related nuclear cataract, in addition to replicating the association at CRYAA, and suggest a strong genetic link between age-related nuclear and congenital cataracts.
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- 2020
3. Identification of genetic effects underlying type 2 diabetes in South Asian and European populations
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Marie Loh, Weihua Zhang, Hong Kiat Ng, Katharina Schmid, Amel Lamri, Lin Tong, Meraj Ahmad, Jung-Jin Lee, Maggie C. Y. Ng, Lauren E. Petty, Cassandra N. Spracklen, Fumihiko Takeuchi, Md. Tariqul Islam, Farzana Jasmine, Anuradhani Kasturiratne, Muhammad Kibriya, Karen L. Mohlke, Guillaume Paré, Gauri Prasad, Mohammad Shahriar, Miao Ling Chee, H. Janaka de Silva, James C. Engert, Hertzel C. Gerstein, K. Radha Mani, Charumathi Sabanayagam, Marijana Vujkovic, Ananda R. Wickremasinghe, Tien Yin Wong, Chittaranjan S. Yajnik, Salim Yusuf, Habibul Ahsan, Dwaipayan Bharadwaj, Sonia S. Anand, Jennifer E. Below, Michael Boehnke, Donald W. Bowden, Giriraj R. Chandak, Ching-Yu Cheng, Norihiro Kato, Anubha Mahajan, Xueling Sim, Mark I. McCarthy, Andrew P. Morris, Jaspal S. Kooner, Danish Saleheen, John C. Chambers, Lee Kong Chian School of Medicine (LKCMedicine), Medical Research Council (MRC), Wellcome Trust, National Institute for Health Research, and Commission of the European Communities
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endocrine system diseases ,Diabetes ,Medicine (miscellaneous) ,Genetic Variation ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Asians ,Asian People ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Humans ,Genetic Predisposition to Disease ,Medicine [Science] ,General Agricultural and Biological Sciences ,Genome-Wide Association Study - Abstract
South Asians are at high risk of developing type 2 diabetes (T2D). We carried out a genome-wide association meta-analysis with South Asian T2D cases (n = 16,677) and controls (n = 33,856), followed by combined analyses with Europeans (neff = 231,420). We identify 21 novel genetic loci for significant association with T2D (P = 4.7 × 10-8 to 5.2 × 10-12), to the best of our knowledge at the point of analysis. The loci are enriched for regulatory features, including DNA methylation and gene expression in relevant tissues, and highlight CHMP4B, PDHB, LRIG1 and other genes linked to adiposity and glucose metabolism. A polygenic risk score based on South Asian-derived summary statistics shows ~4-fold higher risk for T2D between the top and bottom quartile. Our results provide further insights into the genetic mechanisms underlying T2D, and highlight the opportunities for discovery from joint analysis of data from across ancestral populations. Ministry of Health (MOH) National Medical Research Council (NMRC) Published version J.C.C. is supported by the Singapore Ministry of Health’s National Medical Research Council under its Singapore. The SINDI study is supported by the National Medical Research Council (NMRC), Singapore (grants 0796/2003, 1176/2008, 1149/2008, STaR/0003/2008, 1249/2010, CG/ SERI/2010, CIRG/1371/2013, and CIRG/1417/2015), and Biomedical Research Council (BMRC), Singapore (08/1/35/19/550 and 09/1/35/19/616).
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- 2022
4. Singapore Chinese Eye Study: key findings from baseline examination and the rationale, methodology of the 6-year follow-up series
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Wei Dai, Tien Yin Wong, Charumathi Sabanayagam, Ecosse L. Lamoureux, Yih Chung Tham, Miao Li Chee, Miao-Ling Chee, Ching-Yu Cheng, Shivani Majithia, Cong Ling Teo, and Neelam Kumari
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Adult ,Male ,China ,medicine.medical_specialty ,Time Factors ,Eye Diseases ,Fundus Oculi ,Population ,Visual Acuity ,Cellular and Molecular Neuroscience ,Age Distribution ,Singapore chinese ,Risk Factors ,Surveys and Questionnaires ,Epidemiology ,Prevalence ,Humans ,Medicine ,Fluorescein Angiography ,Sex Distribution ,education ,Baseline (configuration management) ,Aged ,Retrospective Studies ,Aged, 80 and over ,Singapore ,education.field_of_study ,business.industry ,Incidence ,Incidence (epidemiology) ,Chinese adults ,Middle Aged ,Sensory Systems ,Low vision ,Ophthalmology ,Cross-Sectional Studies ,Family medicine ,Cohort ,Female ,business ,Tomography, Optical Coherence ,Visually Impaired Persons ,Follow-Up Studies - Abstract
Background/aimsIn order to address the eye care needs of the increasing numbers of elderly Chinese globally, there is a need for comprehensive understanding on the longitudinal trends of age-related eye diseases among Chinese. We herein report the key findings from the baseline Singapore Chinese Eye Study (SCES-1), and describe the rationale and methodology of the 6-year follow-up study (SCES-2).Methods3353 Chinese adults who participated in the baseline SCES-1 (2009–2011) were invited for the 6-year follow-up SCES-2 (2015–2017). Examination procedures for SCES-2 included standardised ocular, systemic examinations and questionnaires identical to SCES-1. SCES-2 further included new examinations such as optical coherence tomography angiography, and questionnaires to evaluate health impact and economic burden of eye diseases.ResultsIn SCES-1, the age-adjusted prevalence of best-corrected low vision (VAConclusionsBuilding on SCES-1, SCES-2 will be one of the few longitudinal population-based eye studies to report incidence, progression, and risk factors of major age-related eye diseases. Findings from this cohort may offer new insights, and provide useful reference information for other Chinese populations elsewhere.
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- 2019
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5. Meta-analysis uncovers genome-wide significant variants for rapid kidney function decline
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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
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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
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- 2021
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6. Cohort Profile: The Singapore Epidemiology of Eye Diseases study (SEED)
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Cong Ling Teo, Zhi Da Soh, Ecosse L. Lamoureux, Shivani Majithia, Simon Nusinovici, Tien Yin Wong, Neelam Kumari, Sahil Thakur, Miao-Li Chee, Ching-Yu Cheng, Charumathi Sabanayagam, Miao-Ling Chee, and Yih Chung Tham
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medicine.medical_specialty ,Singapore ,Eye Diseases ,Epidemiology ,Cross-sectional study ,business.industry ,MEDLINE ,Ethnic group ,General Medicine ,Cohort Studies ,Cross-Sectional Studies ,Risk Factors ,Family medicine ,Cohort ,medicine ,Prevalence ,Humans ,business ,Cohort study - Published
- 2020
7. Plasma lipoprotein subfraction concentrations are associated with lipid metabolism and age-related macular degeneration[S]
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Alfred Tau Liang Gan, Qiao Fan, Ian Yeo, Rajendra S. Apte, Tien Yin Wong, Chiea Chuen Khor, E. Shyong Tai, Ranjana Mathur, Miao Ling Chee, Ching-Yu Cheng, and Chui Ming Gemmy Cheung
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0301 basic medicine ,Male ,medicine.medical_specialty ,Very low-density lipoprotein ,genetic structures ,Lipoproteins ,QD415-436 ,Biochemistry ,Pathogenesis ,03 medical and health sciences ,chemistry.chemical_compound ,Macular Degeneration ,0302 clinical medicine ,Endocrinology ,High-density lipoprotein ,Internal medicine ,Cholesterylester transfer protein ,medicine ,Humans ,genetics ,Research Articles ,Aged ,Polymorphism, Genetic ,biology ,business.industry ,Lipid metabolism ,Cell Biology ,Macular degeneration ,medicine.disease ,eye diseases ,Cholesterol Ester Transfer Proteins ,030104 developmental biology ,Phenotype ,chemistry ,high density lipoprotein ,cholesterylester transfer protein ,Case-Control Studies ,030221 ophthalmology & optometry ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Female ,sense organs ,business ,Lipoprotein ,Chylomicron - Abstract
Disturbance in lipid metabolism has been suggested as a major pathogenic factor for age-related macular degeneration (AMD). Conventional lipid measures have been inconsistently associated with AMD. Other factors that can alter lipid metabolism include lipoprotein phenotype and genetic mutations. We performed a case-control study to examine the association between lipoprotein profile and neovascular AMD (nAMD) and whether the cholesterylester transfer protein (CETP) D442G mutation modulates these associations. Patients with nAMD had significantly higher concentrations of HDL and IDL compared with controls. The increase in HDL particles in nAMD patients was driven by an excess of medium-sized particles. Concurrently, patients with nAMD also had lower Apo A-1, lower VLDL and chylomicron lipoprotein. Many of these associations showed a dose-dependent association between controls, early AMD cases, and nAMD cases. Adjustment for the presence of the D442G mutation at the CETP locus did not significantly alter the increased AMD risk associated with HDL particle concentration. AMD is associated with variation in many lipoprotein subclasses, including increased HDL and IDL particles and decreased Apo A-1, VLDL, and chylomicron particles. These data suggest widespread systemic disturbance in lipid metabolism in the pathogenesis of AMD, including possible alterations in lipoprotein carrier capacity.
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- 2017
8. Corrigendum to: Cohort profile: The Singapore Epidemiology of Eye Diseases Study (SEED)
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Miao-Li Chee, Yih Chung Tham, Neelam Kumari, Miao-Ling Chee, Zhi Da Soh, Simon Nusinovici, Tien Yin Wong, Charumathi Sabanayagam, Shivani Majithia, Cong Ling Teo, Sahil Thakur, Ecosse L. Lamoureux, and Ching-Yu Cheng
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medicine.medical_specialty ,Epidemiology ,business.industry ,Published Erratum ,Family medicine ,Cohort ,medicine ,MEDLINE ,General Medicine ,business - Published
- 2021
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9. Genome-wide association meta-analyses and fine-mapping elucidate pathways influencing albuminuria
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Tobias Hermle, Holger Kirsten, Karsten B. Sieber, Aiko P. J. de Vries, Su Chi Lim, Peter Kovacs, Charumathi Sabanayagam, Carl D. Langefeld, Bernhard K. Krämer, Kent D. Taylor, Janine F. Felix, Belen Ponte, Markus Loeffler, Mary F. Feitosa, Kai-Uwe Eckardt, Jianjun Liu, Katalin Dittrich, Charlene A. Wong, Uwe Völker, Adriana M. Hung, Thomas Meitinger, Anubha Mahajan, Anselm Hoppmann, Erik Ingelsson, Martin H. de Borst, Oscar H. Franco, Niek Verweij, Kai-Uwe Saum, Vilmundur Gudnason, Bram P. Prins, Carsten A. Böger, Terho Lehtimäki, Andrew A. Hicks, Todd L. Edwards, Olivier Devuyst, Peter P. Pramstaller, Katrin Horn, Leslie A. Lange, Johanne Tremblay, Jin-Fang Chai, Sahar Ghasemi, Kjell Nikus, Tanja Poulain, Massimiliano Cocca, Anna Köttgen, Eric Boerwinkle, Barry I. Freedman, Miao-Ling Chee, Man Li, Stephan J. L. Bakker, Tamara B. Harris, Albert V. Smith, Ton J. Rabelink, Dennis O. Mook-Kanamori, Iris M. Heid, Jasmin Divers, Chaolong Wang, Kathleen A. Ryan, Pavel Hamet, Silke Szymczak, Shih-Jen Hwang, Hauke Thomsen, Rainer Rettig, Ayush Giri, Fernando Rivadeneira, Leo-Pekka Lyytikäinen, Cristian Pattaro, Andrej Teren, Valencia Hui Xian Foo, Myriam Rheinberger, Audrey Y. Chu, Barbara McMullen, Franziska Grundner-Culemann, Masayuki Yasuda, Murielle Bochud, Martin Gögele, Anke Tönjes, Jeannette Lee, Adrienne Tin, Kevin Ho, Konstantin Strauch, Josef Coresh, Renée de Mutsert, Sandra Freitag-Wolf, Gardar Sveinbjornsson, Yizhe Xu, Katalin Susztak, Tien Yin Wong, Mary L. Biggs, Isleifur Olafsson, Qiong Yang, Antje Körner, Chengxiang Qiu, E-Shyong Tai, Martina Müller-Nurasyid, Ben Schöttker, Jeffrey O' Connell, Mengmeng Chen, Daniel F. Gudbjartsson, Dermot F. Reilly, Vincent W. V. Jaddoe, Damia Noce, Pim van der Harst, Sanaz Sedaghat, Chiea Chuen Khor, Adam S. Butterworth, Mathias Gorski, Robert J. Carroll, James G. Wilson, Johan Ärnlöv, Christa Meisinger, Kenneth Rice, Bettina Jung, Christian M. Shaffer, Unnur Thorsteinsdottir, Matthias Nauck, Shreeram Akilesh, Mika Kähönen, Johanna Jakobsdottir, Melanie Waldenberger, Ralph Burkhardt, Daniela Baptista, John Danesh, Benjamin B. Sun, Karlhans Endlich, Holly Kramer, Frauke Degenhardt, Wolfgang Lieb, Kari Stefansson, Joachim Thiery, Lars Lind, Nicholette D. Palmer, Sarah A. Pendergrass, Suzanne Vogelezang, Peter J. van der Most, Afshin Parsa, Markus Scholz, Florian Kronenberg, Joseph C. Maranville, Laura M. Raffield, Hermann Brenner, Wieland Kiess, Anna I. Podgornaia, Yuan Shi, Tanguy Corre, Miao-Li Chee, Deborah Mascalzoni, Bamidele O. Tayo, Navya Shilpa Josyula, Ching-Yu Cheng, Lea Gerstner, Nisha Bansal, Jerome I. Rotter, Alexander Teumer, Vilmantas Giedraitis, Raymond Noordam, Ron T. Gansevoort, Lihua Wang, Andrew P. Morris, Bruce M. Psaty, Boting Ning, Zhi Yu, Christian Fuchsberger, Matthias Wuttke, Heiko Runz, Annette Peters, Yih Chung Tham, James P. Cook, Yong Li, Chris H. L. Thio, Hilma Holm, Alessandro De Grandi, Jonathan Marten, André G. Uitterlinden, Andre Franke, Nicholas Y. Q. Tan, Otis D. Wilson, Georg Ehret, Cecilia M. Lindgren, Josyf C. Mychaleckyj, Wolfgang Koenig, Harold Snieder, Michael Stumvoll, Kozeta Miliku, M. Arfan Ikram, Teresa Nutile, Læknadeild (HÍ), Faculty of Medicine (UI), School of Health Sciences (UI), Heilbrigðisvísindasvið (HÍ), Háskóli Íslands, University of Iceland, Teumer, Alexander [0000-0002-8309-094X], Li, Yong [0000-0003-2651-8791], Wuttke, Matthias [0000-0003-3420-5082], Giri, Ayush [0000-0002-7786-4670], Qiu, Chengxiang [0000-0002-6346-8669], Kirsten, Holger [0000-0002-3126-7950], Tin, Adrienne [0000-0002-4207-5866], Feitosa, Mary F. [0000-0002-0933-2410], Chai, Jin-Fang [0000-0003-3770-1137], Cocca, Massimiliano [0000-0002-1127-7596], Gorski, Mathias [0000-0002-9103-5860], Horn, Katrin [0000-0002-5307-6936], Li, Man [0000-0002-3839-0281], Marten, Jonathan [0000-0001-6916-2014], van der Most, Peter J. [0000-0001-8450-3518], Burkhardt, Ralph [0000-0003-1924-1202], Coresh, Josef [0000-0002-4598-0669], de Borst, Martin H. [0000-0002-4127-8733], Ehret, Georg [0000-0002-5730-0675], Endlich, Karlhans [0000-0001-6052-6061], Felix, Janine F. [0000-0002-9801-5774], Franke, Andre [0000-0003-1530-5811], Freedman, Barry I. [0000-0003-0275-5530], Freitag-Wolf, Sandra [0000-0002-1069-7740], Giedraitis, Vilmantas [0000-0003-3423-2021], Grundner-Culemann, Franziska [0000-0001-9649-281X], Gudnason, Vilmundur [0000-0001-5696-0084], Hicks, Andrew A. [0000-0001-6320-0411], Ikram, M. Arfan [0000-0003-0372-8585], Ingelsson, Erik [0000-0003-2256-6972], Jaddoe, Vincent W. V. [0000-0003-2939-0041], Josyula, Navya Shilpa [0000-0003-2782-8812], Khor, Chiea-Chuen [0000-0002-1128-4729], Koenig, Wolfgang [0000-0002-2064-9603], Kovacs, Peter [0000-0002-0290-5423], Kronenberg, Florian [0000-0003-2229-1120], Lindgren, Cecilia M. [0000-0002-4903-9374], Liu, Jianjun [0000-0002-3255-3019], Lyytikäinen, Leo-Pekka [0000-0002-7200-5455], Mahajan, Anubha [0000-0001-5585-3420], Mascalzoni, Deborah [0000-0003-4156-1464], Miliku, Kozeta [0000-0002-9614-7191], Müller-Nurasyid, Martina [0000-0003-3793-5910], Mychaleckyj, Josyf C. [0000-0003-2595-0005], Palmer, Nicholette D. [0000-0001-8883-2511], Poulain, Tanja [0000-0003-3825-5829], Raffield, Laura M. [0000-0002-7892-193X], Rice, Kenneth M. [0000-0002-3071-7278], Rivadeneira, Fernando [0000-0001-9435-9441], Sabanayagam, Charumathi [0000-0002-4042-4719], Smith, Albert V. [0000-0003-1942-5845], Sun, Benjamin B. [0000-0001-6347-2281], Szymczak, Silke [0000-0002-8897-9035], Taylor, Kent D. [0000-0002-2756-4370], Thio, Chris H. L. [0000-0003-2623-7172], Uitterlinden, André G. [0000-0002-7276-3387], van der Harst, Pim [0000-0002-2713-686X], Verweij, Niek [0000-0002-4303-7685], Völker, Uwe [0000-0002-5689-3448], Wang, Chaolong [0000-0003-3945-1012], Yang, Qiong [0000-0002-3658-1375], Devuyst, Olivier [0000-0003-3744-4767], Edwards, Todd L. [0000-0003-4318-6119], Ho, Kevin [0000-0002-3054-8697], Morris, Andrew P. [0000-0002-6805-6014], Pendergrass, Sarah A. [0000-0002-0565-6522], Rotter, Jerome I. [0000-0001-7191-1723], Stefansson, Kari [0000-0003-1676-864X], Susztak, Katalin [0000-0002-1005-3726], Scholz, Markus [0000-0002-4059-1779], Butterworth, Adam S. [0000-0002-6915-9015], Hung, Adriana M. [0000-0002-3203-1608], Pattaro, Cristian [0000-0002-4119-0109], Köttgen, Anna [0000-0002-4671-3714], Apollo - University of Cambridge Repository, Groningen Institute for Organ Transplantation (GIOT), Lifestyle Medicine (LM), Groningen Kidney Center (GKC), Cardiovascular Centre (CVC), Life Course Epidemiology (LCE), Epidemiology, Erasmus MC other, Pediatrics, Internal Medicine, Feitosa, Mary F [0000-0002-0933-2410], van der Most, Peter J [0000-0001-8450-3518], de Borst, Martin H [0000-0002-4127-8733], Felix, Janine F [0000-0002-9801-5774], Freedman, Barry I [0000-0003-0275-5530], Hicks, Andrew A [0000-0001-6320-0411], Ikram, M Arfan [0000-0003-0372-8585], Jaddoe, Vincent WV [0000-0003-2939-0041], Lindgren, Cecilia M [0000-0002-4903-9374], Mychaleckyj, Josyf C [0000-0003-2595-0005], Palmer, Nicholette D [0000-0001-8883-2511], Raffield, Laura M [0000-0002-7892-193X], Rice, Kenneth M [0000-0002-3071-7278], Smith, Albert V [0000-0003-1942-5845], Sun, Benjamin B [0000-0001-6347-2281], Taylor, Kent D [0000-0002-2756-4370], Thio, Chris HL [0000-0003-2623-7172], Uitterlinden, André G [0000-0002-7276-3387], Edwards, Todd L [0000-0003-4318-6119], Morris, Andrew P [0000-0002-6805-6014], Pendergrass, Sarah A [0000-0002-0565-6522], Rotter, Jerome I [0000-0001-7191-1723], Butterworth, Adam S [0000-0002-6915-9015], and Hung, Adriana M [0000-0002-3203-1608]
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0301 basic medicine ,Drosophila melanogaster/genetics ,Diabetes Mellitus/genetics ,LD SCORE REGRESSION ,030232 urology & nephrology ,45/43 ,General Physics and Astronomy ,Genome-wide association study ,BLOOD-PRESSURE ,Bioinformatics ,GLOMERULAR-FILTRATION-RATE ,Genome-wide association studies ,Diabetes mellitus genetics ,0302 clinical medicine ,Creatinine/urine ,Risk Factors ,Genome-wide ,Phenomics ,lcsh:Science ,ddc:616 ,Regulation of gene expression ,RISK ,Gene knockdown ,Kidney diseases ,Multidisciplinary ,HERITABILITY ,Albuminuria/genetics ,article ,Chromosome Mapping ,Kidney disease ,ddc ,3. Good health ,Drosophila melanogaster ,Creatinine ,Nýrnasjúkdómar ,692/4022/1585 ,Slit diaphragm ,Medical genetics ,medicine.symptom ,Erfðarannsóknir ,Medical Genetics ,medicine.medical_specialty ,Science ,631/208/205/2138 ,610 Medicine & health ,Biology ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Meta-Analysis as Topic ,360 Social problems & social services ,Diabetes Mellitus ,medicine ,Animals ,Humans ,Albuminuria ,Genetic Predisposition to Disease ,ddc:610 ,EXCRETION RATE ,CARDIOVASCULAR EVENTS ,Genetic association ,Medicinsk genetik ,TRANS-EQTLS ,KIDNEY-DISEASE ,General Chemistry ,030104 developmental biology ,Gene Expression Regulation ,Genetic Loci ,COLLABORATIVE METAANALYSIS ,lcsh:Q ,Genome-Wide Association Study - Abstract
Publisher's version (útgefin grein)., Increased levels of the urinary albumin-to-creatinine ratio (UACR) are associated with higher risk of kidney disease progression and cardiovascular events, but underlying mechanisms are incompletely understood. Here, we conduct trans-ethnic (n = 564,257) and European-ancestry specific meta-analyses of genome-wide association studies of UACR, including ancestry- and diabetes-specific analyses, and identify 68 UACR-associated loci. Genetic correlation analyses and risk score associations in an independent electronic medical records database (n = 192,868) reveal connections with proteinuria, hyperlipidemia, gout, and hypertension. Fine-mapping and trans-Omics analyses with gene expression in 47 tissues and plasma protein levels implicate genes potentially operating through differential expression in kidney (including TGFB1, MUC1, PRKCI, and OAF), and allow coupling of UACR associations to altered plasma OAF concentrations. Knockdown of OAF and PRKCI orthologs in Drosophila nephrocytes reduces albumin endocytosis. Silencing fly PRKCI further impairs slit diaphragm formation. These results generate a priority list of genes and pathways for translational research to reduce albuminuria., Competing interests: Karsten B. Sieber is full-time employee of GlaxoSmithKline. Gardar Sveinbjornsson, Daniel F. Gudbjartsson, Hilma Holm, Unnur Thorsteinsdottir and Kari Stefansson are full-time employees of deCODE genetics, Amgen Inc. John Danesh is member of the Novartis Cardiovascular and Metabolic Advisory Board, received grant support from Novartis. Oscar H. Franco works in ErasmusAGE, a center for aging research across the life course funded by Nestlé Nutrition (Nestec Ltd.), Metagenics Inc., and AXA. Wolfgang Koenig received modest consultation fees for advisory board meetings from Amgen, DalCor, Kowa, Novartis, Pfizer and Sanofi, and modest personal fees for lectures from Amgen, AstraZeneca, Novartis, Pfizer and Sanofi. Anna I. Podgornaia and Dermot F. Reilly are employees of Merck Sharp Dohme Corp., Whitehouse Station, NJ, USA. Kevin Ho disclosed a research and financial relationship with Sanofi-Genzyme. Bruce M. Psaty serves on the DSMB of a clinical trial funded by the manufacturer (Zoll LifeCor) and on the Steering Committee of the Yale Open Data Access Project funded by Johnson & Johnson. Markus Scholz: Consultancy of and grant support from Merck Serono not related to this project. Adam S. Butterworth received grants from MSD, Pfizer, Novartis, Biogen and Bioverativ and personal fees from Novartis. Anna Köttgen received grant support from Gruenenthal not related to this project. The other authors declare no competing interests.
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- 2019
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10. Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore
- Author
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Degang Wu, Jinzhuang Dou, Xiaoran Chai, Claire Bellis, Andreas Wilm, Chih Chuan Shih, Wendy Wei Jia Soon, Nicolas Bertin, Clarabelle Bitong Lin, Chiea Chuen Khor, Michael DeGiorgio, Shanshan Cheng, Li Bao, Neerja Karnani, William Ying Khee Hwang, Sonia Davila, Patrick Tan, Asim Shabbir, Angela Moh, Eng-King Tan, Jia Nee Foo, Liuh Ling Goh, Khai Pang Leong, Roger S.Y. Foo, Carolyn Su Ping Lam, Arthur Mark Richards, Ching-Yu Cheng, Tin Aung, Tien Yin Wong, Huck Hui Ng, Jianjun Liu, Chaolong Wang, Matthew Andrew Ackers-Johnson, Edita Aliwarga, Kenneth Hon Kim Ban, Denis Bertrand, John C. Chambers, Dana Leng Hui Chan, Cheryl Xue Li Chan, Miao Li Chee, Miao Ling Chee, Pauline Chen, Yunxin Chen, Elaine Guo Yan Chew, Wen Jie Chew, Lynn Hui Yun Chiam, Jenny Pek Ching Chong, Ivan Chua, Stuart A. Cook, Wei Dai, Rajkumar Dorajoo, Chuan-Sheng Foo, Rick Siow Mong Goh, Axel M. Hillmer, Ishak D. Irwan, Fazlur Jaufeerally, Asif Javed, Justin Jeyakani, John Tat Hung Koh, Jia Yu Koh, Pavitra Krishnaswamy, Jyn Ling Kuan, Neelam Kumari, Ai Shan Lee, Seow Eng Lee, Sheldon Lee, Yen Ling Lee, See Ting Leong, Zheng Li, Peter Yiqing Li, Jun Xian Liew, Oi Wah Liew, Su Chi Lim, Weng Khong Lim, Chia Wei Lim, Tingsen Benson Lim, Choon Kiat Lim, Seet Yoong Loh, Au Wing Lok, Calvin W.L. Chin, Shivani Majithia, Sebastian Maurer-Stroh, Wee Yang Meah, Shi Qi Mok, Niranjan Nargarajan, Pauline Ng, Sarah B. Ng, Zhenyuan Ng, Jessica Yan Xia Ng, Ebonne Ng, Shi Ling Ng, Simon Nusinovici, Chin Thing Ong, Bangfen Pan, Vincent Pedergnana, Stanley Poh, Shyam Prabhakar, Kumar M. Prakash, Ivy Quek, Charumathi Sabanayagam, Wei Qiang See, Yee Yen Sia, Xueling Sim, Wey Cheng Sim, Jimmy So, Dinna K.N. Soon, E. Shyong Tai, Nicholas Y. Tan, Louis C.S. Tan, Hong Chang Tan, Wilson Lek Wen Tan, Moses Tandiono, Amanda Tay, Sahil Thakur, Yih Chung Tham, Zenia Tiang, Grace Li-Xian Toh, Pi Kuang Tsai, Lavanya Veeravalli, Chandra S. Verma, Ling Wang, Min Rui Wang, Wing-Cheong Wong, Zhicheng Xie, Khung Keong Yeo, Liang Zhang, Weiwei Zhai, Yi Zhao, Cardiovascular Centre (CVC), Lee Kong Chian School of Medicine (LKCMedicine), and School of Biological Sciences
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Male ,medicine.medical_specialty ,Demographic history ,Population ,Genome-wide association study ,HAPLOTYPE ,Biology ,VARIANTS ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,ANCESTRY ESTIMATION ,03 medical and health sciences ,0302 clinical medicine ,Whole-genome Sequencing ,Asian People ,HISTORY ,medicine ,Humans ,WIDE ASSOCIATION ,Medicine [Science] ,Selection, Genetic ,education ,ADAPTATION ,030304 developmental biology ,Whole genome sequencing ,Singapore ,0303 health sciences ,Genetic diversity ,education.field_of_study ,Whole Genome Sequencing ,Asian Populations ,Genome, Human ,Malaysia ,Human genetics ,GENOTYPE ,MODEL ,Genetics, Population ,Evolutionary biology ,Medical genetics ,Female ,HEALTH ,HUMAN-EVOLUTION ,030217 neurology & neurosurgery ,Imputation (genetics) - Abstract
Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese ∼24,800 years ago and experienced significant admixture with East Asians ∼1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions. Agency for Science, Technology and Research (A*STAR) National Medical Research Council (NMRC) National Research Foundation (NRF) Accepted version We acknowledge H.M. Kang, S. Das, A. Tan, F. Zhang, J. Terhorst, P.-R. Loh, and G. Hellenthal for helpful discussions and support from all participants and clinical research coordinators of the contributing cohorts and studies: the TTSH Healthy Control Workgroup, the SEED cohort, the Asian Sudden Cardiac Death in Heart Failure Study, the Singapore Heart Failure Outcomes and Phenotypes (SHOP) cohort, the Asian neTwork for Translational Research and Cardiovascular Trials (ATTRaCT), the Parkinson’s Disease Study, the Peranakan Genome Study, the Platinum Asian Genomes Project, the Bariatric Surgery Study, the National Heart Centre Singapore Biobank and SingHEART cohorts, and the GUSTO and S-PRESTO study groups. This study was supported by Singapore’s A*STAR (core funding and IAF-PP H17/01/a0/007), BMRC (SPF2014/001, SPF2013/002, SPF2014/003, SPF2014/004, and SPF2014/005), NMRC (CIRG/1371/2013, CIRG/1417/2015, CIRG/1488/ 2018, CSA-SI/0012/2017, CG/017/2013, CG/M006/2017_NHCS, TCR/013- NNI/2014, STaR/0011/2012, STaR2013/001, STaR/014/2013, STaR/0026/ 2015, TCR/006-NUHS/2013, TCR/012-NUHS/2014, TCR/004-NUS/2008, TCR/012-NUHS/2014, and center grants 2010-13 and 2013-2017), NRF (NRFF2016-03), National University of Singapore, SingHealth and DukeNUS, and Alexandra Health small innovative grant SIGII/15203 and funding from Huazhong University of Science and Technology, the Tanoto Foundation, the Lee Foundation, the Boston Scientific Investigator Sponsored Research Program and Bayer, the NSF (DEB-1753489), and the Alfred P. Sloan Foundation. The computation was partially performed on resources of the National Supercomputing Centre, Singapore (https://www.nscc.sg).
- Published
- 2019
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