Partitioning heritability by functional annotation using genome-wide association summary statistics.

Nat Genet
Authors
Keywords
Abstract

Recent work has demonstrated that some functional categories of the genome contribute disproportionately to the heritability of complex diseases. Here we analyze a broad set of functional elements, including cell type-specific elements, to estimate their polygenic contributions to heritability in genome-wide association studies (GWAS) of 17 complex diseases and traits with an average sample size of 73,599. To enable this analysis, we introduce a new method, stratified LD score regression, for partitioning heritability from GWAS summary statistics while accounting for linked markers. This new method is computationally tractable at very large sample sizes and leverages genome-wide information. Our findings include a large enrichment of heritability in conserved regions across many traits, a very large immunological disease-specific enrichment of heritability in FANTOM5 enhancers and many cell type-specific enrichments, including significant enrichment of central nervous system cell types in the heritability of body mass index, age at menarche, educational attainment and smoking behavior.

Year of Publication
2015
Journal
Nat Genet
Volume
47
Issue
11
Pages
1228-35
Date Published
2015 Nov
ISSN
1546-1718
URL
DOI
10.1038/ng.3404
PubMed ID
26414678
PubMed Central ID
PMC4626285
Links
Grant list
F32 GM106584 / GM / NIGMS NIH HHS / United States
R03 CA173785 / CA / NCI NIH HHS / United States
R01 HG006399 / HG / NHGRI NIH HHS / United States
T32 GM007753 / GM / NIGMS NIH HHS / United States
WT098051 / Wellcome Trust / United Kingdom
R21 CA182821 / CA / NCI NIH HHS / United States
MC_UU_12015/2 / Medical Research Council / United Kingdom
MC_U106179472 / Medical Research Council / United Kingdom
U01 HG0070033 / HG / NHGRI NIH HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
R01 MH101244 / MH / NIMH NIH HHS / United States
T32 GM007748 / GM / NIGMS NIH HHS / United States