Tropf, Felix C.; Lee, S. Hong; Verweij, Renske M.; Stulp, Gert; van der Most, Peter J.; de Vlaming, Ronald; Bakshi, Andrew; Briley, Daniel A.; Rahal, Charles; Hellpap, Robert; Iliadou, Anastasia N.; Esko, Tõnu
Meta-analyses of genome-wide association studies, which dominate genetic discovery, are based on data from diverse historical time periods and populations. Genetic scores derived from genome-wide association studies explain only a fraction of the heritability estimates obtained from 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 heterogeneity across sampling populations and time, showing that estimates are substantially smaller across populations compared with within populations. We show that the hidden heritability varies substantially: from zero for height to 20% for body mass index, 37% for education, 40% for age at first birth and up to 75% for number of children. Simulations demonstrate that our results are more likely to reflect heterogeneity in phenotypic measurement or gene–environment interactions than genetic heterogeneity. These findings have substantial implications for genetic discovery, suggesting that large homogenous datasets are required for behavioural phenotypes and that gene–environment interaction may be a central challenge for genetic discovery.
Nature Human Behaviour
Tropf FC, Lee SH, Verweij RM, et al. Hidden heritability due to heterogeneity across seven populations. Nature Human Behaviour. 2017;1(10):757-765. doi:10.1038/s41562-017-0195-1
Tropf, F. C., Lee, S. H., Verweij, R. M., Stulp, G., van der Most, P. J., de Vlaming, R., … Mills, M. C. (2017). Hidden heritability due to heterogeneity across seven populations. Nature Human Behaviour. Springer Nature. https://doi.org/10.1038/s41562-017-0195-1
Tropf, Felix C., S. Hong Lee, Renske M. Verweij, Gert Stulp, Peter J. van der Most, Ronald de Vlaming, Andrew Bakshi, et al. “Hidden Heritability Due to Heterogeneity across Seven Populations.” Nature Human Behaviour. Springer Nature, 2017. https://doi.org/10.1038/s41562-017-0195-1.
F. C. Tropf et al., “Hidden heritability due to heterogeneity across seven populations,” Nature Human Behaviour, vol. 1, no. 10. Springer Nature, pp. 757–765, 2017.
Tropf FC, Lee SH, Verweij RM, Stulp G, van der Most PJ, de Vlaming R, Bakshi A, Briley DA, Rahal C, Hellpap R, Iliadou AN, Esko T, Metspalu A, Medland SE, Martin NG, Barban N, Snieder H, Robinson MR, Mills MC. 2017. Hidden heritability due to heterogeneity across seven populations. Nature Human Behaviour. 1(10), 757–765.
Tropf, Felix C., et al. “Hidden Heritability Due to Heterogeneity across Seven Populations.” Nature Human Behaviour, vol. 1, no. 10, Springer Nature, 2017, pp. 757–65, doi:10.1038/s41562-017-0195-1.