1. Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease
- Author
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Zhao, W., Rasheed, A., Tikkanen, E., Lee, J.J., Butterworth, A.S., Howson, J.M.M., Assimes, T.L., Chowdhury, R., Orho-Melander, M., Damrauer, S., Small, A., Asma, S., Imamura, M., Yamauch, T., Chambers, J.C., Chen, P., Sapkota, B.R., Shah, N., Jabeen, S., Surendran, P., Lu, Y.C., Zhang, W.H., Imran, A., Abbas, S., Majeed, F., Trindade, K., Qamar, N., Mallick, N.H., Yaqoob, Z., Saghir, T., Rizvi, S.N.H., Memon, A., Rasheed, S.Z., Memon, F.U.R., Mehmood, K., Ahmed, N., Qureshi, I.H., Tanveer-us-Salam, Iqbal, W., Malik, U., Mehra, N., Kuo, J.Z., Sheu, W.H.H., Guo, X.Q., Hsiung, C.A., Juang, J.M.J., Taylor, K.D., Hung, Y.J., Lee, W.J., Quertermous, T., Lee, I.T., Hsu, C.C., Bottinger, E.P., Ralhan, S., Teo, Y.Y., Wang, T.D., Alam, D.S., Angelantonio, E. di, Epstein, S., Nielsen, S.F., Nordestgaard, B.G., Tybjaerg-Hansen, A., Young, R., Benn, M., Frikke-Schmidt, R., Kamstrup, P.R., Biobank, M., Jukema, J.W., Sattar, N., Smit, R., Chung, R.H., Liang, K.W., Anand, S., Sanghera, D.K., Ripatti, S., Loos, R.J.F., Kooner, J.S., Tai, E.S., Rotter, J.I., Chen, Y.D.I., Frossard, P., Maeda, S., Kadowaki, T., Reilly, M., Pare, G., Melander, O., Salomaa, V., Rader, D.J., Danesh, J., Voight, B.F., Saleheen, D., CHD Exome Consortium, EPIC-CVD Consortium, EPIC-Interact Consortium, Butterworth, Adam [0000-0002-6915-9015], Howson, Joanna [0000-0001-7618-0050], Chowdhury, Rajiv [0000-0003-4881-5690], Surendran, Praveen [0000-0002-4911-6077], Di Angelantonio, Emanuele [0000-0001-8776-6719], Danesh, John [0000-0003-1158-6791], and Apollo - University of Cambridge Repository
- Subjects
0301 basic medicine ,endocrine system diseases ,EPIC-Interact Consortium ,Genome-wide association study ,Coronary Disease ,Type 2 diabetes ,ACID-BINDING PROTEIN ,Comorbidity ,030204 cardiovascular system & hematology ,VARIANTS ,Cardiovascular ,Bioinformatics ,Medical and Health Sciences ,0302 clinical medicine ,Risk Factors ,2.1 Biological and endogenous factors ,ARTERY-DISEASE ,Molecular Targeted Therapy ,Aetiology ,health care economics and organizations ,11 Medical and Health Sciences ,Genetics & Heredity ,RISK ,Metabolic Syndrome ,0303 health sciences ,CHD Exome+ Consortium ,Diabetes ,Single Nucleotide ,Biological Sciences ,3. Good health ,Europe ,Heart Disease ,MENDELIAN RANDOMIZATION ,Medical genetics ,Life Sciences & Biomedicine ,Type 2 ,Metabolic Networks and Pathways ,Asian Continental Ancestry Group ,medicine.medical_specialty ,endocrine system ,Asia ,education ,European Continental Ancestry Group ,Mutation, Missense ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,EPIC-CVD Consortium ,GENETIC ARCHITECTURE ,03 medical and health sciences ,Asian People ,Clinical Research ,Mendelian randomization ,Diabetes Mellitus ,Genetics ,Genetic predisposition ,medicine ,Humans ,Genetic Predisposition to Disease ,Obesity ,Genetic variability ,cardiovascular diseases ,Polymorphism ,GENOME-WIDE ASSOCIATION ,Heart Disease - Coronary Heart Disease ,Metabolic and endocrine ,METAANALYSIS ,AP2 ,030304 developmental biology ,Science & Technology ,Human Genome ,nutritional and metabolic diseases ,Odds ratio ,06 Biological Sciences ,medicine.disease ,HLA-DRB5 Chains ,Michigan Biobank ,030104 developmental biology ,ATHEROSCLEROSIS ,Diabetes Mellitus, Type 2 ,Genetic Loci ,Mutation ,Missense ,human activities ,Biomarkers ,Genome-Wide Association Study ,Developmental Biology - Abstract
Danish Saleheen, Benjamin Voight and colleagues perform genome-wide analysis of multi-ancestry cohorts to identify genetic associations with type 2 diabetes (T2D) and coronary heart disease (CHD). They find novel loci and show that 24% of T2D loci are also associated with CHD and that greater genetic risk of T2D increases risk of CHD. 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.
- Published
- 2017