MedStar Authors catalog › Details for: Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.
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Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease.

by Epstein, Stephen E.
Citation: Nature Genetics. 49(10):1450-1457, 2017 Oct.Journal: Nature genetics; Nature genetics.Published: 2017ISSN: 1061-4036.Full author list: Zhao W; Rasheed A; Tikkanen E; Lee JJ; Butterworth AS; Howson JMM; Assimes TL; Chowdhury R; Orho-Melander M; Damrauer S; Small A; Asma S; Imamura M; Yamauch T; Chambers JC; Chen P; Sapkota BR; Shah N; Jabeen S; Surendran P; Lu Y; Zhang W; Imran A; Abbas S; Majeed F; Trindade K; Qamar N; Mallick NH; Yaqoob Z; Saghir T; Rizvi SNH; Memon A; Rasheed SZ; Memon FU; Mehmood K; Ahmed N; Qureshi IH; Tanveer-Us-Salam; Iqbal W; Malik U; Mehra N; Kuo JZ; Sheu WH; Guo X; Hsiung CA; Juang JJ; Taylor KD; Hung YJ; Lee WJ; Quertermous T; Lee IT; Hsu CC; Bottinger EP; Ralhan S; Teo YY; Wang TD; Alam DS; Di Angelantonio E; Epstein S; Nielsen SF; Nordestgaard BG; Tybjaerg-Hansen A; Young R; CHD Exome+ Consortium; Benn M; Frikke-Schmidt R; Kamstrup PR; EPIC-CVD Consortium; EPIC-Interact Consortium; Michigan Biobank; Jukema JW; Sattar N; Smit R; Chung RH; Liang KW; Anand S; Sanghera DK; Ripatti S; Loos RJF; Kooner JS; Tai ES; Rotter JI; Chen YI; Frossard P; Maeda S; Kadowaki T; Reilly M; Pare G; Melander O; Salomaa V; Rader DJ; Danesh J; Voight BF; Saleheen D.UI/PMID: 28869590.Subject(s): Asia/ep [Epidemiology] | Asian Continental Ancestry Group/ge [Genetics] | Biomarkers | Comorbidity | Coronary Disease/ep [Epidemiology] | Coronary Disease/et [Etiology] | *Coronary Disease/ge [Genetics] | Diabetes Mellitus, Type 2/dt [Drug Therapy] | Diabetes Mellitus, Type 2/ep [Epidemiology] | Diabetes Mellitus, Type 2/et [Etiology] | *Diabetes Mellitus, Type 2/ge [Genetics] | Europe/ep [Epidemiology] | European Continental Ancestry Group/ge [Genetics] | Genetic Loci/ge [Genetics] | Genetic Predisposition to Disease | *Genome-Wide Association Study | HLA-DRB5 Chains/ge [Genetics] | Humans | Metabolic Networks and Pathways/ge [Genetics] | Metabolic Syndrome X/ep [Epidemiology] | Metabolic Syndrome X/ge [Genetics] | Molecular Targeted Therapy | Mutation, Missense | Polymorphism, Single Nucleotide | Risk FactorsInstitution(s): MedStar Health Research InstituteActivity type: Journal Article.Medline article type(s): Journal ArticleDigital Object Identifier: https://dx.doi.org/10.1038/ng.3943 (Click here) Abbreviated citation: Nat Genet. 49(10):1450-1457, 2017 Oct.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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