作者
Farhad Hormozdiari, Steven Gazal, Bryce Van De Geijn, Hilary K Finucane, Chelsea J-T Ju, Po-Ru Loh, Armin Schoech, Yakir Reshef, Xuanyao Liu, Luke O’connor, Alexander Gusev, Eleazar Eskin, Alkes L Price
发表日期
2018/7
期刊
Nature genetics
卷号
50
期号
7
页码范围
1041-1047
出版商
Nature Publishing Group US
简介
There is increasing evidence that many risk loci found using genome-wide association studies are molecular quantitative trait loci (QTLs). Here we introduce a new set of functional annotations based on causal posterior probabilities of fine-mapped molecular cis-QTLs, using data from the Genotype-Tissue Expression (GTEx) and BLUEPRINT consortia. We show that these annotations are more strongly enriched for heritability (5.84× for eQTLs; P = 1.19 × 10−31) across 41 diseases and complex traits than annotations containing all significant molecular QTLs (1.80× for expression (e)QTLs). eQTL annotations obtained by meta-analyzing all GTEx tissues generally performed best, whereas tissue-specific eQTL annotations produced stronger enrichments for blood- and brain-related diseases and traits. eQTL annotations restricted to loss-of-function intolerant genes were even more enriched for heritability (17.06× …
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