Assortative mating biases marker-based heritability estimators

• Published in: Nature communications Vol. 13; no. 1; pp. 660 - 10
• Main Authors: Border, Richard, O’Rourke, Sean, de Candia, Teresa, Goddard, Michael E., Visscher, Peter M., Yengo, Loic, Jones, Matt, Keller, Matthew C.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 03.02.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208/1515; 631/208/457; Algorithms; Assortative mating; Bias; Biobanks; Computer Simulation; Equilibrium; Estimates; Estimators; Female; Genetic factors; Genetics, Population - methods; Genome-Wide Association Study - methods; Genomes; Genotype & phenotype; Heritability; Humanities and Social Sciences; Humans; Influence; Likelihood Functions; Linkage Disequilibrium; Male; Markers; Mate selection; Mathematical models; Mating; Mendelian Randomization Analysis - methods; Models, Genetic; multidisciplinary; Phenotype; Polymorphism, Single Nucleotide; Production methods; Quantitative genetics; Quantitative Trait, Heritable; Reproduction - genetics; Science; Science (multidisciplinary)
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-022-28294-9

Many traits are subject to assortative mating, with recent molecular genetic findings confirming longstanding theoretical predictions that assortative mating induces long range dependence across causal variants. However, all marker-based heritability estimators implicitly assume mating is random. We provide mathematical and simulation-based evidence demonstrating that both method-of-moments and likelihood-based estimators are biased in the presence of assortative mating and derive corrected heritability estimators for traits subject to assortment. Finally, we demonstrate that the empirical patterns of estimates across methods and sample sizes for real traits subject to assortative mating are congruent with expected assortative mating-induced biases. For example, marker-based heritability estimates for height are 14% – 23% higher than corrected estimates using UK Biobank data. Methods for estimating heritability, the fraction of variance attributable to genetic factors, assume random mating. Here, the authors show that under assortative mating, when mate choice reflects phenotypic similarity, these methods produce overestimates.