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

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 correlat...

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Bibliographic Details
Published in:	Science (American Association for the Advancement of Science) 2022-11, Vol.378 (6621), p.754-761
Main Authors:	Border, Richard, Athanasiadis, Georgios, Buil, Alfonso, Schork, Andrew J, Cai, Na, Young, Alexander I, Werge, Thomas, Flint, Jonathan, Kendler, Kenneth S, Sankararaman, Sriram, Dahl, Andy W, Zaitlen, Noah A
Format:	Article
Language:	eng
Subjects:	Assortative mating Cell Communication Genetic relationship Genome-Wide Association Study Humans Mental disorders Multifactorial Inheritance Phenotype Phenotypes
Online Access:	Get full text
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Summary:	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 ( =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.
ISSN:	0036-8075 1095-9203