Journal
NATURE GENETICS
Volume 49, Issue 7, Pages 986-+Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/ng.3865
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Funding
- UK Medical Research Council [MR/L012561/1]
- British Heart Foundation [RG/10/12/28456]
- Imperial College NIHR Biomedical Research Centre (BRC)
- NIHR Cambridge Biomedical Research Centre
- [49228-1]
- MRC [MR/L012561/1] Funding Source: UKRI
- British Heart Foundation [SP/13/6/30554, RG/10/12/28456] Funding Source: researchfish
- National Institute for Health Research [NF-SI-0515-10091] Funding Source: researchfish
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SNP heritability, the proportion of phenotypic variance explained by SNPs, has been reported for many hundreds of traits. Its estimation requires strong prior assumptions about the distribution of heritability across the genome, but current assumptions have not been thoroughly tested. By analyzing imputed data for a large number of human traits, we empirically derive a model that more accurately describes how heritability varies with minor allele frequency (MAF), linkage disequilibrium (LD) and genotype certainty. Across 19 traits, our improved model leads to estimates of common SNP heritability on average 43% (s. d. 3%) higher than those obtained from the widely used software GCTA and 25% (s. d. 2%) higher than those from the recently proposed extension GCTA-LDMS. Previously, DNase I hypersensitivity sites were reported to explain 79% of SNP heritability; using our improved heritability model, their estimated contribution is only 24%.
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