Adipose Tissue Gene Expression Associations Reveal Hundreds of Candidate Genes for Cardiometabolic Traits.
GWAS
adipocyte
colocalization
diabetes
eQTL
lipid
obesity
secondary signal
trans-ancestry
waist-hip ratio
Journal
American journal of human genetics
ISSN: 1537-6605
Titre abrégé: Am J Hum Genet
Pays: United States
ID NLM: 0370475
Informations de publication
Date de publication:
03 10 2019
03 10 2019
Historique:
received:
29
05
2019
accepted:
03
09
2019
pubmed:
1
10
2019
medline:
3
4
2020
entrez:
1
10
2019
Statut:
ppublish
Résumé
Genome-wide association studies (GWASs) have identified thousands of genetic loci associated with cardiometabolic traits including type 2 diabetes (T2D), lipid levels, body fat distribution, and adiposity, although most causal genes remain unknown. We used subcutaneous adipose tissue RNA-seq data from 434 Finnish men from the METSIM study to identify 9,687 primary and 2,785 secondary cis-expression quantitative trait loci (eQTL; <1 Mb from TSS, FDR < 1%). Compared to primary eQTL signals, secondary eQTL signals were located further from transcription start sites, had smaller effect sizes, and were less enriched in adipose tissue regulatory elements compared to primary signals. Among 2,843 cardiometabolic GWAS signals, 262 colocalized by LD and conditional analysis with 318 transcripts as primary and conditionally distinct secondary cis-eQTLs, including some across ancestries. Of cardiometabolic traits examined for adipose tissue eQTL colocalizations, waist-hip ratio (WHR) and circulating lipid traits had the highest percentage of colocalized eQTLs (15% and 14%, respectively). Among alleles associated with increased cardiometabolic GWAS risk, approximately half (53%) were associated with decreased gene expression level. Mediation analyses of colocalized genes and cardiometabolic traits within the 434 individuals provided further evidence that gene expression influences variant-trait associations. These results identify hundreds of candidate genes that may act in adipose tissue to influence cardiometabolic traits.
Identifiants
pubmed: 31564431
pii: S0002-9297(19)30340-4
doi: 10.1016/j.ajhg.2019.09.001
pmc: PMC6817527
pii:
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
773-787Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK072193
Pays : United States
Organisme : NHLBI NIH HHS
ID : P01 HL028481
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK062370
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009937
Pays : United States
Organisme : NIGMS NIH HHS
ID : R25 GM055336
Pays : United States
Organisme : NIDDK NIH HHS
ID : P30 DK020572
Pays : United States
Organisme : NCI NIH HHS
ID : P01 CA142538
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK105561
Pays : United States
Organisme : NIDDK NIH HHS
ID : R01 DK093757
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL127921
Pays : United States
Organisme : NIEHS NIH HHS
ID : P30 ES010126
Pays : United States
Organisme : Intramural NIH HHS
ID : ZIA HG000024
Pays : United States
Organisme : NHGRI NIH HHS
ID : R01 HG009974
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM067553
Pays : United States
Organisme : NIDDK NIH HHS
ID : U01 DK062370
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007092
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH118349
Pays : United States
Organisme : NHLBI NIH HHS
ID : F31 HL146121
Pays : United States
Informations de copyright
Copyright © 2019 American Society of Human Genetics. All rights reserved.
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