TY - JOUR
T1 - Partitioning heritability by functional annotation using genome-wide association summary statistics
AU - Finucane, Hilary K
AU - Bulik-Sullivan, Brendan
AU - Gusev, Alexander
AU - Trynka, Gosia
AU - Reshef, Yakir
AU - Loh, Po-Ru
AU - Anttila, Verneri
AU - Xu, Han
AU - Zang, Chongzhi
AU - Farh, Kyle
AU - Ripke, Stephan
AU - Day, Felix R
AU - ReproGen Consortium
AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium
AU - The RACI Consortium
AU - Purcell, Shaun
AU - Stahl, Eli
AU - Lindstrom, Sara
AU - Perry, John R B
AU - Okada, Yukinori
AU - Raychaudhuri, Soumya
AU - Daly, Mark J
AU - Patterson, Nick
AU - Neale, Benjamin M
AU - Price, Alkes L
AU - Stolk, Lisette
AU - Visser, Jenny A.
AU - Uitterlinden, André
AU - Rivadeneira, Fernando
AU - van Meurs, Joyce
AU - Hofman, Bert
AU - Laven, Joop
PY - 2015/11
Y1 - 2015/11
N2 - 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.
AB - 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.
U2 - 10.1038/ng.3404
DO - 10.1038/ng.3404
M3 - Article
C2 - 26414678
SN - 1061-4036
VL - 47
SP - 1228
EP - 1235
JO - Nature Genetics
JF - Nature Genetics
IS - 11
ER -