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A global overview of pleiotropy and genetic architecture in complex traits.

Authors :
Watanabe K
Stringer S
Frei O
Umićević Mirkov M
de Leeuw C
Polderman TJC
van der Sluis S
Andreassen OA
Neale BM
Posthuma D
Source :
Nature genetics [Nat Genet] 2019 Sep; Vol. 51 (9), pp. 1339-1348. Date of Electronic Publication: 2019 Aug 19.
Publication Year :
2019

Abstract

After a decade of genome-wide association studies (GWASs), fundamental questions in human genetics, such as the extent of pleiotropy across the genome and variation in genetic architecture across traits, are still unanswered. The current availability of hundreds of GWASs provides a unique opportunity to address these questions. We systematically analyzed 4,155 publicly available GWASs. For a subset of well-powered GWASs on 558 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 these overlap with loci from multiple traits. We find that potential causal variants are enriched in coding and flanking regions, as well as in regulatory elements, and show variation in polygenicity and discoverability of traits. Our results provide insights into how genetic variation contributes to trait variation. All GWAS results can be queried and visualized at the GWAS ATLAS resource ( https://atlas.ctglab.nl ).

Details

Language :
English
ISSN :
1546-1718
Volume :
51
Issue :
9
Database :
MEDLINE
Journal :
Nature genetics
Publication Type :
Academic Journal
Accession number :
31427789
Full Text :
https://doi.org/10.1038/s41588-019-0481-0