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Cross-trait assortative mating is widespread and inflates genetic correlation estimates.
Science 378, 754-761 (2022)
The observation of genetic correlations between disparate human traits has been interpreted as evidence of widespread pleiotropy. Here, we introduce cross-trait assortative mating (xAM) as an alternative explanation. We observe that xAM affects many phenotypes and that phenotypic cross-mate correlation estimates are strongly associated with genetic correlation estimates (R2 = 74%). We demonstrate that existing xAM plausibly accounts for substantial fractions of genetic correlation estimates and that previously reported genetic correlation estimates between some pairs of psychiatric disorders are congruent with xAM alone. Finally, we provide evidence for a history of xAM at the genetic level using cross-trait even/odd chromosome polygenic score correlations. Together, our results demonstrate that previous reports have likely overestimated the true genetic similarity between many phenotypes.
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Publication type
Article: Journal article
Document type
Scientific Article
Keywords
Ld Score Regression; Heritability
ISSN (print) / ISBN
0036-8075
e-ISSN
1095-9203
Journal
Science
Quellenangaben
Volume: 378,
Issue: 6621,
Pages: 754-761
Publisher
American Association for the Advancement of Science (AAAS)
Publishing Place
1200 New York Ave, Nw, Washington, Dc 20005 Usa
Non-patent literature
Publications
Reviewing status
Peer reviewed
Institute(s)
Helmholtz Pioneer Campus (HPC)
Grants
Wellcome Trust
NCI NIH HHS
NIEHS NIH HHS
NHLBI NIH HHS
NIGMS NIH HHS
NINDS NIH HHS
NIMH NIH HHS
NHGRI NIH HHS
NIA NIH HHS
NCI NIH HHS
NIEHS NIH HHS
NHLBI NIH HHS
NIGMS NIH HHS
NINDS NIH HHS
NIMH NIH HHS
NHGRI NIH HHS
NIA NIH HHS