Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease
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Peer-reviewed
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Abstract
To evaluate the shared genetic etiology of type 2 diabetes (T2D) and coronary heart disease (CHD), we conducted a genome-wide, multi-ancestry study of genetic variation for both diseases in up to 265,678 subjects for T2D and 260,365 subjects for CHD. We identify 16 previously unreported loci for T2D and 1 locus for CHD, including a new T2D association at a missense variant in HLA-DRB5 (odds ratio (OR) = 1.29). We show that genetically mediated increase in T2D risk also confers higher CHD risk. Joint T2D–CHD analysis identified eight variants—two of which are coding—where T2D and CHD associations appear to colocalize, including a new joint T2D–CHD association at the CCDC92 locus that also replicated for T2D. The variants associated with both outcomes implicate new pathways as well as targets of existing drugs, including icosapent ethyl and adipocyte fatty-acid-binding protein.
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1546-1718
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European Commission and European Federation of Pharmaceutical Industries and Associations (EFPIA) FP7 Innovative Medicines Initiative (IMI) (116074)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC)
British Heart Foundation (CH/12/2/29428)
Medical Research Council (MR/P013880/1)
Ume� University (unknown)
NHS Blood and Transplant (NHSBT) (WP12-01)
European Commission (279143)
NHS Blood and Transplant (NHSBT) (11-01-GEN)
Cambridge University Hospitals NHS Foundation Trust (CUH) (BRC 2012-2017)
British Heart Foundation (None)
Medical Research Council (MR/L003120/1)
European Commission (279233)
European Research Council (268834)
MRC (MR/J015709/1)
MRC (MR/J006602/1)
MRC (MR/J006599/1)
Medical Research Council (MR/M012816/1)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
Cambridge University Hospitals NHS Foundation Trust (CUH) (146281)
British Heart Foundation (RG/16/4/32218)
Cambridge University Hospitals NHS Foundation Trust (CUH) (3819-1617-25)
Department of Health (via National Institute for Health Research (NIHR)) (NIHR BTRU-2014-10024)
Cambridge University Hospitals NHS Foundation Trust (CUH) (3819-1516-29)
Cambridge University Hospitals NHS Foundation Trust (CUH) (unknown)
National Institute of Neurological Disorders and Stroke (R21NS064908)
Medical Research Council (G0800270)
British Heart Foundation (None)
National Heart Lung and Blood Institute (RC2HL101834)
Fogarty International Center (RC1TW008485)
Medical Research Council (G0800270/1)