RT Journal Article
SR Electronic
T1 Regulatory variants explain much more heritability than coding variants across 11 common diseases
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 004309
DO 10.1101/004309
A1 Alexander Gusev
A1 S. Hong Lee
A1 Benjamin M. Neale
A1 Gosia Trynka
A1 Bjarni J. Vilhjálmsson
A1 Hilary Finucane
A1 Han Xu
A1 Chongzhi Zang
A1 Stephan Ripke
A1 Eli Stahl
A1 Schizophrenia Working Group of the Psychiatric Genomics Consortium
A1 SWE-SCZ Consortium
A1 Anna K. Kähler
A1 Christina M. Hultman
A1 Shaun M. Purcell
A1 Steven A. McCarroll
A1 Mark Daly
A1 Bogdan Pasaniuc
A1 Patrick F. Sullivan
A1 Naomi R. Wray
A1 Soumya Raychaudhuri
A1 Alkes L. Price
YR 2014
UL http://biorxiv.org/content/early/2014/04/20/004309.abstract
AB Common variants implicated by genome-wide association studies (GWAS) of complex diseases are known to be enriched for coding and regulatory variants. We applied methods to partition the heritability explained by genotyped SNPs across functional categories (while accounting for shared variance due to linkage disequilibrium) to genotype and imputed data for 11 common diseases. DNaseI Hypersensitivity Sites (DHS) from 218 cell-types, spanning 16% of the genome, explained an average of 79% of (5.1× enrichment; P < 10−20); further enrichment was observed at enhancer and cell-type specific DHS elements. The enrichments were much smaller in analyses that did not use imputed data or were restricted to GWAS-associated SNPs. In contrast, coding variants, spanning 1% of the genome, explained only 8% of enrichment; P = 5 × 10−4). We replicated these findings but found no significant contribution from rare coding variants in an independent schizophrenia cohort genotyped on GWAS and exome chips.