TY - JOUR
T1 - A global overview of pleiotropy and genetic architecture in complex traits
AU - Watanabe, Kyoko
AU - Stringer, Sven
AU - Frei, Oleksandr
AU - Umićević Mirkov, Maša
AU - de Leeuw, Christiaan
AU - Polderman, Tinca J. C.
AU - van der Sluis, Sophie
AU - Andreassen, Ole A.
AU - Neale, Benjamin M.
AU - Posthuma, Danielle
N1 - Funding Information:
We thank all consortiums and all other individual laboratories for making GWAS summary statistics publicly available. We also thank P. Visscher and N. Wray for their thoughtful suggestions and discussions. We additionally thank A. Dale for his suggestions. This work was funded by the Netherlands Organization for Scientific Research (grant nos. NWO VICI 453-14-005 and NWO VIDI 452-12-014).
Publisher Copyright:
© 2019, The Author(s), under exclusive licence to Springer Nature America, Inc.
Copyright:
Copyright 2019 Elsevier B.V., All rights reserved.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - 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).
AB - 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).
UR - https://www.scopus.com/pages/publications/85071079806
U2 - 10.1038/s41588-019-0481-0
DO - 10.1038/s41588-019-0481-0
M3 - Article
C2 - 31427789
SN - 1061-4036
VL - 51
SP - 1339
EP - 1348
JO - Nature genetics
JF - Nature genetics
IS - 9
ER -