--- _id: '7728' abstract: - lang: eng text: '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.' article_processing_charge: No article_type: original author: - first_name: Felix C. full_name: Tropf, Felix C. last_name: Tropf - first_name: S. Hong full_name: Lee, S. Hong last_name: Lee - first_name: Renske M. full_name: Verweij, Renske M. last_name: Verweij - first_name: Gert full_name: Stulp, Gert last_name: Stulp - first_name: Peter J. full_name: van der Most, Peter J. last_name: van der Most - first_name: Ronald full_name: de Vlaming, Ronald last_name: de Vlaming - first_name: Andrew full_name: Bakshi, Andrew last_name: Bakshi - first_name: Daniel A. full_name: Briley, Daniel A. last_name: Briley - first_name: Charles full_name: Rahal, Charles last_name: Rahal - first_name: Robert full_name: Hellpap, Robert last_name: Hellpap - first_name: Anastasia N. full_name: Iliadou, Anastasia N. last_name: Iliadou - first_name: Tõnu full_name: Esko, Tõnu last_name: Esko - first_name: Andres full_name: Metspalu, Andres last_name: Metspalu - first_name: Sarah E. full_name: Medland, Sarah E. last_name: Medland - first_name: Nicholas G. full_name: Martin, Nicholas G. last_name: Martin - first_name: Nicola full_name: Barban, Nicola last_name: Barban - first_name: Harold full_name: Snieder, Harold last_name: Snieder - first_name: Matthew Richard full_name: Robinson, Matthew Richard id: E5D42276-F5DA-11E9-8E24-6303E6697425 last_name: Robinson orcid: 0000-0001-8982-8813 - first_name: Melinda C. full_name: Mills, Melinda C. last_name: Mills citation: ama: 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 apa: 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 chicago: 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. ieee: 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. ista: 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. mla: 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. short: F.C. Tropf, S.H. Lee, R.M. Verweij, G. Stulp, P.J. van der Most, R. de Vlaming, A. Bakshi, D.A. Briley, C. Rahal, R. Hellpap, A.N. Iliadou, T. Esko, A. Metspalu, S.E. Medland, N.G. Martin, N. Barban, H. Snieder, M.R. Robinson, M.C. Mills, Nature Human Behaviour 1 (2017) 757–765. date_created: 2020-04-30T10:47:02Z date_published: 2017-09-11T00:00:00Z date_updated: 2021-01-12T08:15:08Z day: '11' doi: 10.1038/s41562-017-0195-1 extern: '1' intvolume: ' 1' issue: '10' language: - iso: eng month: '09' oa_version: None page: 757-765 publication: Nature Human Behaviour publication_identifier: issn: - 2397-3374 publication_status: published publisher: Springer Nature quality_controlled: '1' status: public title: Hidden heritability due to heterogeneity across seven populations type: journal_article user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87 volume: 1 year: '2017' ...