RT Journal Article
SR Electronic
T1 A global overview of pleiotropy and genetic architecture in complex traits
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 500090
DO 10.1101/500090
A1 Watanabe, Kyoko
A1 Stringer, Sven
A1 Frei, Oleksandr
A1 Mirkov, Maša Umićević
A1 Polderman, Tinca J.C.
A1 van der Sluis, Sophie
A1 Andreassen, Ole A.
A1 Neale, Benjamin M.
A1 Posthuma, Danielle
YR 2018
UL http://biorxiv.org/content/early/2018/12/19/500090.abstract
AB After a decade of genome-wide association studies (GWASs), fundamental questions in human genetics are still unanswered, such as the extent of pleiotropy across the genome, the nature of trait-associated genetic variants and the disparate genetic architecture across human traits. The current availability of hundreds of GWAS results provide the unique opportunity to gain insight into these questions. In this study, we harmonized and systematically analysed 4,155 publicly available GWASs. For a subset of well-powered GWAS on 558 unique traits, we provide an extensive overview of pleiotropy and genetic architecture. We show that trait associated loci cover more than half of the genome, and 90% of those loci are associated with multiple trait domains. We further show that potential causal genetic variants are enriched in coding and flanking regions, as well as in regulatory elements, and how trait-polygenicity is related to an estimate of the required sample size to detect 90% of causal genetic variants. Our results provide novel insights into how genetic variation contributes to trait variation. All GWAS results can be queried and visualized at the GWAS ATLAS resource (http://atlas.ctglab.nl).