Limited statistical evidence for shared genetic effects of eQTLs and autoimmune-disease-associated loci in three major immune-cell types.

TitleLimited statistical evidence for shared genetic effects of eQTLs and autoimmune-disease-associated loci in three major immune-cell types.
Publication TypeJournal Article
Year of Publication2017
AuthorsChun, S, Casparino, A, Patsopoulos, NA, Croteau-Chonka, DC, Raby, BA, De Jager, PL, Sunyaev, SR, Cotsapas, C
JournalNat Genet
Volume49
Issue4
Pagination600-605
Date Published2017 Apr
ISSN1546-1718
Abstract

Most autoimmune-disease-risk effects identified by genome-wide association studies (GWAS) localize to open chromatin with gene-regulatory activity. GWAS loci are also enriched in expression quantitative trait loci (eQTLs), thus suggesting that most risk variants alter gene expression. However, because causal variants are difficult to identify, and cis-eQTLs occur frequently, it remains challenging to identify specific instances of disease-relevant changes to gene regulation. Here, we used a novel joint likelihood framework with higher resolution than that of previous methods to identify loci where autoimmune-disease risk and an eQTL are driven by a single shared genetic effect. Using eQTLs from three major immune subpopulations, we found shared effects in only ∼25% of the loci examined. Thus, we show that a fraction of gene-regulatory changes suggest strong mechanistic hypotheses for disease risk, but we conclude that most risk mechanisms are not likely to involve changes in basal gene expression.

DOI10.1038/ng.3795
Alternate JournalNat. Genet.
PubMed ID28218759
PubMed Central IDPMC5374036
Grant ListR01 GM078598 / GM / NIGMS NIH HHS / United States
UL1 TR001863 / TR / NCATS NIH HHS / United States
R01 GM105857 / GM / NIGMS NIH HHS / United States
R01 MH084676 / MH / NIMH NIH HHS / United States
R01 MH101244 / MH / NIMH NIH HHS / United States
U01 HG009088 / HG / NHGRI NIH HHS / United States