Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease

• 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 HLADRB5 (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. © 2017 Nature America, Inc., part of Springer Nature. All rights reserved.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Basic Medicine -- Medical Genetics (hsv//eng)

Nyckelord

fatty acid binding protein 4

icosapentaenoic acid ethyl ester

biological marker

HLA DRB5 antigen

Article

CCDC92 gene

controlled study

East Asian

European

gene

gene locus

genetic risk

genetic susceptibility

genetic variability

genetic variation

genome-wide association study

HLA DRB5 gene

human

ischemic heart disease

major clinical study

non insulin dependent diabetes mellitus

priority journal

single nucleotide polymorphism

South Asian

Asia

Asian continental ancestry group

Caucasian

comorbidity

comparative study

Coronary Disease

Diabetes Mellitus, Type 2

Europe

genetic predisposition

genetics

metabolic syndrome X

metabolism

missense mutation

molecularly targeted therapy

risk factor

Asian Continental Ancestry Group

Biomarkers

Comorbidity

European Continental Ancestry Group

Genetic Loci

Genetic Predisposition to Disease

Genome-Wide Association Study

HLA-DRB5 Chains

Humans

Metabolic Networks and Pathways

Metabolic Syndrome X

Molecular Targeted Therapy

Mutation, Missense

Polymorphism, Single Nucleotide

Risk Factors

Publikations- och innehållstyp

art (ämneskategori)

ref (ämneskategori)