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

Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt

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.

OriginalsprogEngelsk
TidsskriftScience
Vol/bind378
Udgave nummer6621
Sider (fra-til)754-761
Antal sider8
ISSN0036-8075
DOI
StatusUdgivet - 2022

Bibliografisk note

Funding Information:
Chan Zuckerberg Initiative grant CZF2019-002449 (N.A.Z., R.B.), NIH grant R01AG042568 (A.I.Y.), NIH grant R01CA227237 (N.A.Z., R.B.), NIH grant R01CA227466 (N.A.Z., R.B.), NIH grant R01ES029929 (N.A.Z., R.B.), NIH grant R01GM142112 (N.A.Z., R.B.), NIH grant R01HG006399 (N.A.Z., R.B.), NIH grant R01HG011345 (N.A.Z., R.B.), NIH grant R01HL151152 (N.A.Z., R.B.), NIH grant R01HL155024 (N.A.Z., R.B.), NIH grant R01MH125252 (N.A.Z., R.B.), NIH grant R01MH122688 (N.A.Z., R.B.), NIH grant R01MH130581 (A.W.D., J.F., K.S.K., N.A.Z., N.C.), NIH grant R24AG065184 (A.I.Y.), NIH grant R35GM125055 (S.S.), NIH grant R35GM133531 (N.A.Z., R.B.), NIH grant T32NS048004 (R.B.), NIH grant U01MH126798 (N.A.Z., R.B.), NIH grant U01HG009080 (N.A.Z., R.B.), National Science Foundation award CAREER-1943497 (S.S.), Open Philanthropy grant 010623-00001 (A.I.Y.), Wellcome Trust grant 200176/Z/15/Z (J.F., K.S.K.).

Publisher Copyright:
© 2022 American Association for the Advancement of Science. All rights reserved.

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