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

Richard Border, Georgios Athanasiadis, Alfonso Buil, Andrew J Schork, Na Cai, Alexander I Young, Thomas Werge, Jonathan Flint, Kenneth S Kendler, Sriram Sankararaman, Andy W Dahl, Noah A Zaitlen

Abstract

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 ( R 2 = 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.

Original languageEnglish
JournalScience
Volume378
Issue number6621
Pages (from-to)754-761
Number of pages8
ISSN0036-8075
DOIs
Publication statusPublished - 18 Nov 2022

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