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

Area of Science:

• Human genetics
• Behavioral genetics
• Quantitative genetics

Background:

• Genetic correlations between human traits are often attributed to pleiotropy, where one gene influences multiple traits.
• However, alternative explanations for observed genetic correlations require investigation to avoid overestimating genetic similarity.

Purpose of the Study:

• To introduce and evaluate cross-trait assortative mating (xAM) as an alternative explanation for genetic correlations.
• To assess the extent to which xAM can account for observed genetic correlations between human traits, including psychiatric disorders.

Main Methods:

• Phenotypic cross-mate correlation estimation.
• Association analysis between phenotypic cross-mate correlations and genetic correlation estimates.
• Cross-trait even/odd chromosome polygenic score correlations to detect historical xAM.

Main Results:

• Cross-trait assortative mating (xAM) affects numerous phenotypes and is strongly associated with genetic correlation estimates (R²=74%).
• Existing xAM plausibly explains significant portions of genetic correlation estimates.
• Genetic correlations between some psychiatric disorders are consistent with xAM alone, and evidence suggests a history of xAM at the genetic level.

Conclusions:

• Cross-trait assortative mating (xAM) is a significant factor contributing to genetic correlations between human traits.
• Previous estimates of genetic similarity between phenotypes may have been overestimated due to overlooking the effects of xAM.
• Further research into xAM is crucial for accurate interpretation of genetic correlation studies.