Within-family heritability estimates for behavioural and disease phenotypes from 500,000 sibling pairs of diverse ancestries

Abstract

Quantification of the direct effect of genetic variation on human behavioural traits is important for understanding between-individual variation in socioeconomic and health outcomes but estimates of their heritability can be biased by between-family indirect genetic effects. By contrast, using within-family variation in DNA sharing is robust to most confounding factors including shared environmental effects and population stratification. Yet, accurate estimates for most traits are not available using this design, and none for non-European ancestry populations. Here we analyse approximately 500,000 sibling pairs with diverse genetic ancestries and obtain within-family heritability estimates for 14 phenotypes, including two well-studied model traits: height (0.70 ± 0.03) and BMI (0.49 ± 0.03). For behaviour, we find significant within-family heritability for smoking initiation (0.34 ± 0.05), alcohol consumption (0.18 ± 0.04), number of children (0.27 ± 0.11) and personality ('talk versus listen', 0.48 ± 0.13). In addition, we estimated large heritability for type 2 diabetes (0.43 ± 0.06) and asthma (0.34 ± 0.06), whose risk factors include behavioural traits. Overall, we show concordant estimates across ancestry groups and highlight a significant contribution of shared environmental effects for behaviour and type 2 diabetes risk, which may have inflated between-family estimates. Altogether, our results provide within-family evidence that genetic variation is associated with variation in complex traits, common disease and exposures. Our heritability estimates are concordant across genetic ancestries, lower than those from twin-based studies, yet larger than has been accounted for by genome-wide association studies so far.