Contrasting the genetic architecture of 30 complex traits from summary association data

Variance components methods that estimate the aggregate contribution of large sets of variants to the heritability of complex traits have yielded important insights into the disease architecture of common diseases. Here, we introduce new methods that estimate the total variance in trait explained by a single locus in the genome (local heritability) from summary GWAS data while accounting for linkage disequilibrium (LD) among variants. We apply our new estimator to ultra large-scale GWAS summary data of 30 common traits and diseases to gain insights into their local genetic architecture. First, we find that common SNPs have a high contribution to the heritability of all studied traits. Second, we identify traits for which the majority of the SNP heritability can be confined to a small percentage of the genome. Third, we identify GWAS risk loci where the entire locus explains significantly more variance in the trait than the GWAS reported variants. Finally, we identify 55 loci that explain a large proportion of heritability across multiple traits.