Disease Heritability Enrichment of Regulatory Elements Is Concentrated in Elements with Ancient Sequence Age and Conserved Function across Species.

ABSTRACT: Regulatory elements, e.g., enhancers and promoters, have been widely reported to be enriched for disease and complex trait heritability. We investigated how this enrichment varies with the age of the underlying genome sequence, the conservation of regulatory function across species, and the target gene of the regulatory element. We estimated heritability enrichment by applying stratified LD score regression to summary statistics from 41 independent diseases and complex traits (average N = 320K) and meta-analyzing results across traits. Enrichment of human putative enhancers and promoters was larger in elements with older sequence age, assessed via alignment with other species irrespective of conserved functionality: putative enhancer elements with ancient sequence age (older than the split

SUBMITTER: Hujoel MLA 

PROVIDER: S-EPMC6451699 | biostudies-literature | 2019 Apr

REPOSITORIES: biostudies-literature