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

• DOI: 10.1126/science.abo2059
• Publication Date: 2022-11-17T18:58:33Z
• Authors: Richard Border; Georgios Athanasi...; 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
• Keywords: 570; Multifactorial Inheritance; General Science & Technology; Biological Psychology; Human Genome; 610; Cell Communication; Biological Sciences; Phenotype; Genetics; Psychology; Humans; Mental health; Genome-Wide Association Study

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.