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.

MEDICIN OCH HÄLSOVETENSKAP Medicinska och farmaceutiska grundvetenskaper Medicinsk genetik hsv//swe
MEDICAL AND HEALTH SCIENCES Basic Medicine Medical Genetics hsv//eng
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

Rasheed, AsifCentre for Non-Communicable Diseases (författare)
Tikkanen, EmmiUniversity of Helsinki (författare)
Lee, Jung-JinUniversity of Pennsylvania (författare)
Butterworth, Adam S.University of Cambridge (författare)
Howson, Joanna M. M.University of Cambridge (författare)
Orho-Melander, MarjuLund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups(Swepub:lu)endo-mor (författare)
Melander, OlleLund University,Lunds universitet,Kardiovaskulär forskning - hypertoni,Forskargrupper vid Lunds universitet,Cardiovascular Research - Hypertension,Lund University Research Groups(Swepub:lu)endo-ome (författare)
University of PennsylvaniaCentre for Non-Communicable Diseases (creator_code:org_t)

Ingår i:Nature Genetics: Springer Science and Business Media LLC49:10, s. 1450-14571546-17181061-4036

Av författaren/redakt...: Zhao, Wei; Rasheed, Asif; Tikkanen, Emmi; Lee, Jung-Jin; Butterworth, Ada ...; Howson, Joanna M ...; visa fler...; Orho-Melander, M ...; Melander, Olle; visa färre...

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