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

Author:

Border Richard123ORCID,Athanasiadis Georgios45ORCID,Buil Alfonso46ORCID,Schork Andrew J.467ORCID,Cai Na8ORCID,Young Alexander I.9ORCID,Werge Thomas4610ORCID,Flint Jonathan11ORCID,Kendler Kenneth S.12ORCID,Sankararaman Sriram21314ORCID,Dahl Andy W.15ORCID,Zaitlen Noah A.11314ORCID

Affiliation:

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 ( 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.

Publisher

American Association for the Advancement of Science (AAAS)

Subject

Multidisciplinary

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