PT  - JOURNAL ARTICLE
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
TI  - Regulatory variants explain much more heritability than coding variants across 11 common diseases
AID  - 10.1101/004309
DP  - 2014 Jan 01
TA  - bioRxiv
PG  - 004309
4099  - http://biorxiv.org/content/early/2014/04/20/004309.short
4100  - http://biorxiv.org/content/early/2014/04/20/004309.full
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.