Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases

A Gusev; SH Lee; G Trynka; H Finucane; BJ Vilhjálmsson; H Xu; C Zang; S Ripke; B Bulik-Sullivan; E Stahl; AK Kähler; CM Hultman; SM Purcell; SA McCarroll; MJ Daly; B Pasaniuc; PF Sullivan; BM Neale; NR Wray; S Raychaudhuri; AL Price; A Corvin; JTR Walters; KH Farh; PA Holmans; P Lee; DA Collier; H Huang; TH Pers; I Agartz; E Agerbo; M Albus; M Alexander; F Amin; SA Bacanu; M Begemann; RA Belliveau; J Bene; SE Bergen; E Bevilacqua; TB Bigdeli; DW Black; AD Børglum; R Bruggeman; NG Buccola; RL Buckner; W Byerley; W Cahn; G Cai; D Campion; RM Cantor; VJ Carr; N Carrera; SV Catts; KD Chambert; RCK Chan; RYL Chen; EYH Chen; W Cheng; EFC Cheung; SA Chong; CR Cloninger; D Cohen; N Cohen; P Cormican; N Craddock; JJ Crowley; D Curtis; M Davidson; KL Davis; F Degenhardt; J Del Favero; LE De Lisi; D Demontis; D Dikeos; T Dinan; S Djurovic; G Donohoe; E Drapeau; J Duan; F Dudbridge; N Durmishi; P Eichhammer; J Eriksson; V Escott-Price; L Essioux; AH Fanous; MS Farrell; J Frank; L Franke; R Freedman; NB Freimer; M Friedl; JI Friedman; M Fromer; G Genovese; L Georgieva; ES Gershon; I Giegling; P Giusti-Rodrguez

Journal article

Partitioning heritability of regulatory and cell-type-specific variants across 11 common diseases

A Gusev, SH Lee, G Trynka, H Finucane, BJ Vilhjálmsson, H Xu, C Zang, S Ripke, B Bulik-Sullivan, E Stahl, AK Kähler, CM Hultman, SM Purcell, SA McCarroll, MJ Daly, B Pasaniuc, PF Sullivan, BM Neale, NR Wray, S Raychaudhuri Show all

American Journal of Human Genetics | Published : 2014

DOI: 10.1016/j.ajhg.2014.10.004

Abstract

Regulatory and coding variants are known to be enriched with associations identified by genome-wide association studies (GWASs) of complex disease, but their contributions to trait heritability are currently unknown. We applied variance-component methods to imputed genotype data for 11 common diseases to partition the heritability explained by genotyped SNPs (hg 2) across functional categories (while accounting for shared variance due to linkage disequilibrium). Extensive simulations showed that in contrast to current estimates from GWAS summary statistics, the variance-component approach partitions heritability accurately under a wide range of complex-disease architectures. Across the 11 di..

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University of Melbourne Researchers

Eric Yu Hai Chen Author

Christos Pantelis Author

Grants

Awarded by Nederlandse Organisatie voor Wetenschappelijk Onderzoek

Funding Acknowledgements

This study made use of data generated by the Wellcome Trust Case Control Consortium (WTCCC) and the Wellcome Trust Sanger Institute. A full list of the investigators who contributed to the generation of the WTCCC data is available at www.wtccc.org.uk. Funding for the WTCCC project was provided by the Wellcome Trust under award 076113. We thank Manolis Kellis, Abhishek Sarkar, Joe Pickrell, X. Shirley Liu, Nick Patterson, Sara Lindstrom, Peter Kraft, and Shamil Sunyaev for helpful discussions and Amy Williams for assistance with HApI-UR. This research was funded by NIH grants R01 MH101244, R03 HG006731, and 1U01HG0070033, the Doris Duke Clinical Scientist Development Award, and NIH fellowship F32 GM106584. G.T. was supported by the Rubicon grant from the Netherlands Organization for Scientific Research. H.F. was supported by the Fannie and John Hertz Foundation. We also acknowledge grant funding from the Australian Research Council (DE130100614 and FT0991360) and the National Health and Medical Research Council (613602 and 1050218).