Cross-trait assortative mating is widespread and inflates genetic correlation estimates.
Cross-trait assortative mating is widespread and inflates genetic correlation estimates.
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跨性向分类的交配是广泛的，并且膨胀了遗传相关估计。
DOI：
10.1126/science.abo2059
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发表时间：
2022-11-18
期刊：
影响因子：
56.9
通讯作者：
Zaitlen, Noah A.
中科院分区：
文献类型：
--
作者：
Border, Richard;Athanasiadis, Georgios;Buil, Alfonso;Schork, Andrew J.;Cai, Na;Young, Alexander I.;Werge, Thomas;Flint, Jonathan;Kendler, Kenneth S.;Sankararaman, Sriram;Dahl, Andy W.;Zaitlen, Noah A.
对不同人类特征之间遗传相关性的观察已被解释为广泛多效性的证据。在这里，我们引入跨性状选型交配（xAM）作为另一种解释。我们观察到xAM影响许多表型，表型交叉交配相关估计与遗传相关估计密切相关（R2 = 74%）。我们证明，现有的xAM合理地解释了遗传相关估计的很大一部分，并且以前报道的一些精神疾病对之间的遗传相关估计与xAM单独一致。最后，我们利用交叉性状偶/奇染色体多基因评分相关性为xAM在遗传水平上的历史提供了证据。总之，我们的结果表明，以前的报告可能高估了许多表型之间的真实遗传相似性。非随机交配造成的统计伪像，而不是共同的生物学，可能解释了报告的遗传相关性。
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. Statistical artifacts due to non-random mating, rather than shared biology, may explain reported genetic correlations.
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