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The genome-wide association studies (GWAS) dominating genetic discovery are based on large meta-analyses that combine data from diverse historical time periods and populations. Polygenic scores constructed from GWAS explain only a fraction of the heritability derived from twin and whole-genome studies on single-populations, known as the ‘hidden heritability’ puzzle. Using seven sampling populations (N=35,062), we test whether hidden heritability is attributed to genetic heterogeneity, showing that estimates are substantially and generally smaller from across compared to within populations. We show that the hidden SNP-based heritability ranges from zero (height), 20% (BMI), 37% (education), 40% (age at first birth) to 75% (number of children). Simulations demonstrate that our results more likely reflect heterogeneity in phenotypic measurement or gene-environment interaction than genetic explanations. These findings have substantial implications for gene discovery, suggesting that large homogenous datasets are required for behavioural phenotypes and that gene-environment interaction is a central challenge for genetic discovery.


Journal article


Nature Human Behaviour

Publication Date



reproduction, hidden heritability, missing heritability, gene-environment interaction