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Border, R.* ; Athanasiadis, G.I.* ; Buil, A.* ; Schork, A.J.* ; Cai, N. ; Young, A.I.* ; Werge, T.* ; Flint, J.* ; Kendler, K.S.* ; Sankararaman, S.* ; Dahl, A.W.* ; Zaitlen, N.A.*

Cross-trait assortative mating is widespread and inflates genetic correlation estimates.

Science 378, 754-761 (2022)
Publ. Version/Full Text Postprint Research data DOI PMC
Open Access Green
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
Language english
Publication Year 2022
HGF-reported in Year 2022
ISSN (print) / ISBN 0036-8075
e-ISSN 1095-9203
Journal Science
Quellenangaben Volume: 378, Issue: 6621, Pages: 754-761 Article Number: , Supplement: ,
Publisher American Association for the Advancement of Science (AAAS)
Publishing Place 1200 New York Ave, Nw, Washington, Dc 20005 Usa
Reviewing status Peer reviewed
Institute(s) Helmholtz Pioneer Campus (HPC)
POF-Topic(s) 30202 - Environmental Health
Research field(s) Pioneer Campus
PSP Element(s) G-510007-001
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
DOI 10.1126/science.abo2059
WOS ID 001061773500001
Scopus ID 85142175532
PubMed ID 36395242
Erfassungsdatum 2022-12-07
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