Identification of new susceptibility loci for type 2 diabetes and shared etiological pathways with coronary heart disease
Author(s)
Type
Journal Article
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.
Date Issued
2017-09-04
Date Acceptance
2017-08-03
Citation
Nature Genetics, 2017, 49 (10), pp.1450-+
ISSN
1061-4036
Publisher
Nature Research
Start Page
1450
End Page
+
Journal / Book Title
Nature Genetics
Volume
49
Issue
10
Copyright Statement
© 2017 Nature America, Inc., part of Springer Nature. All rights reserved. The final publication is available at Springer via https://doi.org/10.1038/ng.3943
Identifier
http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000411855800008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
Subjects
Science & Technology
Life Sciences & Biomedicine
Genetics & Heredity
ACID-BINDING PROTEIN
GENOME-WIDE ASSOCIATION
MENDELIAN RANDOMIZATION
ARTERY-DISEASE
GENETIC ARCHITECTURE
METAANALYSIS
VARIANTS
RISK
AP2
ATHEROSCLEROSIS
Publication Status
Published
Date Publish Online
2017-09-04