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Identification of genetic effects underlying type 2 diabetes in South Asian and European populations.
Loh, Marie; Zhang, Weihua; Ng, Hong Kiat; Schmid, Katharina; Lamri, Amel; Tong, Lin; Ahmad, Meraj; Lee, Jung-Jin; Ng, Maggie C Y; Petty, Lauren E; Spracklen, Cassandra N; Takeuchi, Fumihiko; Islam, Md Tariqul; Jasmine, Farzana; Kasturiratne, Anuradhani; Kibriya, Muhammad; Mohlke, Karen L; Paré, Guillaume; Prasad, Gauri; Shahriar, Mohammad; Chee, Miao Ling; de Silva, H Janaka; Engert, James C; Gerstein, Hertzel C; Mani, K Radha; Sabanayagam, Charumathi; Vujkovic, Marijana; Wickremasinghe, Ananda R; Wong, Tien Yin; Yajnik, Chittaranjan S; Yusuf, Salim; Ahsan, Habibul; Bharadwaj, Dwaipayan; Anand, Sonia S; Below, Jennifer E; Boehnke, Michael; Bowden, Donald W; Chandak, Giriraj R; Cheng, Ching-Yu; Kato, Norihiro; Mahajan, Anubha; Sim, Xueling; McCarthy, Mark I; Morris, Andrew P; Kooner, Jaspal S; Saleheen, Danish; Chambers, John C.
Affiliation
  • Loh M; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore.
  • Zhang W; Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
  • Ng HK; Department of Epidemiology and Biostatistics, Imperial College London, London, W2 1PG, UK.
  • Schmid K; Department of Cardiology, Ealing Hospital, London North West Healthcare NHS Trust, Middlesex, UB1 3HW, UK.
  • Lamri A; Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, 308232, Singapore.
  • Tong L; Institute of Computational Biology, Deutsches Forschungszentrum für Gesundheit und Umwelt, Helmholtz Zentrum München, 85764, Neuherberg, Germany.
  • Ahmad M; Department of Informatics, Technical University of Munich, 85748, Garching bei München, Neuherberg, Germany.
  • Lee JJ; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Ng MCY; Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
  • Petty LE; The University of Chicago, Biological Sciences Division, Public Health Sciences, 5841 South Maryland Avenue, MC2000, Chicago, IL, 60637, USA.
  • Spracklen CN; Genomic Research on Complex diseases, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India.
  • Takeuchi F; Translational Medicine and Human Genetics, Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
  • Islam MT; Department of Medicine, Mayo Hospital, Lahore, Pakistan.
  • Jasmine F; Center for Genomics and Personalized Medicine Research, Center for Diabetes Research, Wake Forest School of Medicine, Winston-Salem, NC, 37215, USA.
  • Kasturiratne A; Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
  • Kibriya M; Vanderbilt Genetics Institute, Division of Genetic Medicine, Vanderbilt University Medical Center, Nashville, TN, 37232, USA.
  • Mohlke KL; Human Genetics Center, School of Public Health, The University of Texas Health Science Center at Houston, Houston, TX, 77030, USA.
  • Paré G; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Prasad G; Department of Biostatistics and Epidemiology, University of Massachusetts, Amherst, MA, 01003, USA.
  • Shahriar M; Department of Gene Diagnostics and Therapeutics, Research Institute, National Center for Global Health and Medicine, Tokyo, Japan.
  • Chee ML; U Chicago Research Bangladesh, House#4, Road#2b, Sector#4, Uttara, Dhaka, 1230, Bangladesh.
  • de Silva HJ; The University of Chicago, Biological Sciences Division, Public Health Sciences, 5841 South Maryland Avenue, MC2000, Chicago, IL, 60637, USA.
  • Engert JC; Department of Public Health, Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka.
  • Gerstein HC; The University of Chicago, Biological Sciences Division, Public Health Sciences, 5841 South Maryland Avenue, MC2000, Chicago, IL, 60637, USA.
  • Mani KR; Department of Genetics, University of North Carolina at Chapel Hill, Chapel Hill, NC, 27599, USA.
  • Sabanayagam C; Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
  • Vujkovic M; Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada.
  • Wickremasinghe AR; Academy of Scientific and Innovative Research, CSIR-Institute of Genomics and Integrative Biology Campus, New Delhi, 110020, India.
  • Wong TY; Systems Genomics Laboratory, School of Biotechnology, Jawaharlal Nehru University, New Delhi, 110067, India.
  • Yajnik CS; The University of Chicago, Biological Sciences Division, Public Health Sciences, 5841 South Maryland Avenue, MC2000, Chicago, IL, 60637, USA.
  • Yusuf S; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
  • Ahsan H; Department of Medicine, Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka.
  • Bharadwaj D; Department of Medicine, McGill University, Montreal, QC, Canada.
  • Anand SS; Department of Human Genetics, McGill University, Montreal, QC, Canada.
  • Below JE; Department of Medicine, McMaster University, Hamilton, ON, Canada.
  • Boehnke M; Population Health Research Institute, Hamilton Health Sciences and McMaster University, Hamilton, ON, Canada.
  • Bowden DW; Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada.
  • Chandak GR; Genomic Research on Complex diseases, CSIR-Centre for Cellular and Molecular Biology (CSIR-CCMB), Hyderabad, India.
  • Cheng CY; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
  • Kato N; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
  • Mahajan A; Department of Biostatistics and Epidemiology, University of Pennsylvania, Philadelphia, Pennsylvania, 19104, USA.
  • Sim X; Department of Public Health, Faculty of Medicine, University of Kelaniya, Kelaniya, Sri Lanka.
  • McCarthy MI; Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore.
  • Morris AP; Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, Singapore, Singapore.
  • Kooner JS; Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.
  • Saleheen D; Diabetes Unit, King Edward Memorial Hospital and Research Centre, Pune, India.
  • Chambers JC; Department of Medicine, McMaster University, Hamilton, ON, Canada.
Commun Biol ; 5(1): 329, 2022 04 07.
Article in En | MEDLINE | ID: mdl-35393509
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.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus, Type 2 / Genome-Wide Association Study Type of study: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Commun Biol Year: 2022 Document type: Article Affiliation country:
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Diabetes Mellitus, Type 2 / Genome-Wide Association Study Type of study: Diagnostic_studies / Observational_studies / Prognostic_studies / Risk_factors_studies / Systematic_reviews Limits: Humans Language: En Journal: Commun Biol Year: 2022 Document type: Article Affiliation country: