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

doi:10.1126/science.abo2059

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

Science. 2022 Nov 18;378(6621):754-761. doi: 10.1126/science.abo2059. Epub 2022 Nov 17.

Authors

Richard Border^{1

2

3}, Georgios Athanasiadis^{4

5}, Alfonso Buil^{4

6}, Andrew J Schork^{4

6

7}, Na Cai⁸, Alexander I Young⁹, Thomas Werge^{4

6

10}, Jonathan Flint¹¹, Kenneth S Kendler¹², Sriram Sankararaman^{2

13

14}, Andy W Dahl¹⁵, Noah A Zaitlen^{1

13

14}

Affiliations

¹ Department of Neurology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
² Department of Computer Science, University of California, Los Angeles, Los Angeles, CA 90095, USA.
³ Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA 02115, USA.
⁴ Institute of Biological Psychiatry, Mental Health Center Sct Hans, Copenhagen University Hospital-Mental Health Services CPH, 2100 Copenhagen, Denmark.
⁵ Department of Evolutionary Biology, Ecology, and Environmental Sciences, University of Barcelona, 08028 Barcelona, Spain.
⁶ Globe Institute, University of Copenhagen, 1350 Copenhagen, Denmark.
⁷ Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, AZ 85004, USA.
⁸ Helmholtz Pioneer Campus, Helmholtz Zentrum München, 85764 Neuherberg, Germany.
⁹ Anderson School of Management, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁰ Department of Clinical Medicine, University of Copenhagen, 1165 Copenhagen, Denmark.
¹¹ Center for Neurobehavioral Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹² Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA 23298, USA.
¹³ Department of Human Genetics, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁴ Department of Computational Medicine, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA 90095, USA.
¹⁵ Section of Genetic Medicine, Department of Medicine, University of Chicago, Chicago, IL 60637, USA.

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 (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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Cell Communication
Genome-Wide Association Study*
Humans
Multifactorial Inheritance*
Phenotype

Abstract

Publication types

MeSH terms

Grants and funding