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

被引：161

作者：

Chun, Sung ^{[1
,2
,3
,4
]}

Casparino, Alexandra ^{[5
]}

Patsopoulos, Nikolaos A. ^{[3
,4
,6
,7
]}

Croteau-Chonka, Damien C. ^{[2
,8
]}

Raby, Benjamin A. ^{[2
,8
]}

De Jager, Philip L. ^{[2
,3
,4
,6
,7
]}

Sunyaev, Shamil R. ^{[1
,2
,3
,4
,9
]}

Cotsapas, Chris ^{[3
,4
,5
,10
]}

机构：

[1] Brigham & Womens Hosp, Div Genet, 75 Francis St, Boston, MA 02115 USA

[2] Harvard Med Sch, Dept Med, Boston, MA USA

[3] Broad Inst Harvard, Cambridge, MA 02139 USA

[4] MIT, Cambridge, MA 02139 USA

[5] Yale Sch Med, Dept Neurol, New Haven, CT USA

[6] Brigham & Womens Hosp, Dept Neurol, Boston, MA 02115 USA

[7] Brigham & Womens Hosp, Ann Romney Ctr Neurol Dis, Boston, MA 02115 USA

[8] Brigham & Womens Hosp, Channing Div Network Med, Boston, MA 02115 USA

[9] Harvard Med Sch, Dept Biomed Informat, Boston, MA USA

[10] Yale Sch Med, Dept Genet, New Haven, CT USA

来源：

NATURE GENETICS | 2017年 / 49卷 / 04期

关键词：

GENOME-WIDE ASSOCIATION; PARTITIONING HERITABILITY; VARIANTS; TRAITS; COLOCALIZATION; EXPRESSION; GWAS; INTEGRATION; SIGNALS;

D O I：

10.1038/ng.3795

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

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(1,2). 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 similar to 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.

引用

页码：600 / +

页数：9

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