TY - JOUR T1 - Regulatory variants explain much more heritability than coding variants across 11 common diseases JF - bioRxiv DO - 10.1101/004309 SP - 004309 AU - Alexander Gusev AU - S. Hong Lee AU - Benjamin M. Neale AU - Gosia Trynka AU - Bjarni J. Vilhjálmsson AU - Hilary Finucane AU - Han Xu AU - Chongzhi Zang AU - Stephan Ripke AU - Eli Stahl AU - Schizophrenia Working Group of the Psychiatric Genomics Consortium AU - SWE-SCZ Consortium AU - Anna K. Kähler AU - Christina M. Hultman AU - Shaun M. Purcell AU - Steven A. McCarroll AU - Mark Daly AU - Bogdan Pasaniuc AU - Patrick F. Sullivan AU - Naomi R. Wray AU - Soumya Raychaudhuri AU - Alkes L. Price Y1 - 2014/01/01 UR - http://biorxiv.org/content/early/2014/04/20/004309.abstract N2 - 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. ER -