Publication

Hidden heritability due to heterogeneity across seven populations

Tropf, F. C., Lee, S. H., Verweij, R. M., Stulp, G., van der Most, P. J., de Vlaming, R., Bakshi, A., Briley, D. A., Rahal, C., Hellpap, R., Nyman, A., Esko, T., Metspalu, A., Medland, S. E., Martin, N. G., Barban, N., Snieder, H., Robinson, M. R. & Mills, M. C., Oct-2017, In : Nature Human Behaviour. 1, 10, p. 757-765 9 p.

Research output: Contribution to journalArticleAcademicpeer-review

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, 1(10), 757-765. https://doi.org/10.1038/s41562-017-0195-1

Author

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 ; Nyman, Anastasia ; Esko, Tõnu ; Metspalu, Andres ; Medland, Sarah E ; Martin, Nicholas G ; Barban, Nicola ; Snieder, Harold ; Robinson, Matthew R ; Mills, Melinda C. / Hidden heritability due to heterogeneity across seven populations. In: Nature Human Behaviour. 2017 ; Vol. 1, No. 10. pp. 757-765.

Harvard

Tropf, FC, Lee, SH, Verweij, RM, Stulp, G, van der Most, PJ, de Vlaming, R, Bakshi, A, Briley, DA, Rahal, C, Hellpap, R, Nyman, A, 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, vol. 1, no. 10, pp. 757-765. https://doi.org/10.1038/s41562-017-0195-1

Standard

Hidden heritability due to heterogeneity across seven populations. / 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; Nyman, Anastasia; Esko, Tõnu; Metspalu, Andres; Medland, Sarah E; Martin, Nicholas G; Barban, Nicola; Snieder, Harold; Robinson, Matthew R; Mills, Melinda C.

In: Nature Human Behaviour, Vol. 1, No. 10, 10.2017, p. 757-765.

Research output: Contribution to journalArticleAcademicpeer-review

Vancouver

Tropf FC, Lee SH, Verweij RM, Stulp G, van der Most PJ, de Vlaming R et al. Hidden heritability due to heterogeneity across seven populations. Nature Human Behaviour. 2017 Oct;1(10):757-765. https://doi.org/10.1038/s41562-017-0195-1


BibTeX

@article{7ef50cf2e2eb41ea9668fd8c4fc38e13,
title = "Hidden heritability due to heterogeneity across seven populations",
abstract = "Meta-analyses of genome-wide association studies (GWAS), which dominate genetic discovery are based on data from diverse historical time periods and populations. Genetic scores derived from GWAS 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 from across compared to within populations. We show that the hidden heritability varies substantially: from zero (height), to 20{\%} for BMI, 37{\%} for education, 40{\%} for age at first birth and up to 75{\%} for number of children. Simulations demonstrate that our results more likely reflect heterogeneity in phenotypic measurement or gene-environment interaction 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.",
keywords = "Journal Article, BODY-MASS INDEX, GENOME-WIDE ASSOCIATION, COMMON SNPS EXPLAIN, MISSING HERITABILITY, HUMAN HEIGHT, EDUCATIONAL-ATTAINMENT, GENETIC-VARIATION, COMPLEX DISEASES, LARGE PROPORTION, FERTILITY",
author = "Tropf, {Felix C} and Lee, {S Hong} and Verweij, {Renske M} and Gert Stulp and {van der Most}, {Peter J} and {de Vlaming}, Ronald and Andrew Bakshi and Briley, {Daniel A} and Charles Rahal and Robert Hellpap and Anastasia Nyman and T{\~o}nu Esko and Andres Metspalu and Medland, {Sarah E} and Martin, {Nicholas G} and Nicola Barban and Harold Snieder and Robinson, {Matthew R} and Mills, {Melinda C}",
year = "2017",
month = "10",
doi = "10.1038/s41562-017-0195-1",
language = "English",
volume = "1",
pages = "757--765",
journal = "Nature Human Behaviour",
issn = "2397-3374",
publisher = "Nature Publishing Group",
number = "10",

}

RIS

TY - JOUR

T1 - Hidden heritability due to heterogeneity across seven populations

AU - Tropf, Felix C

AU - Lee, S Hong

AU - Verweij, Renske M

AU - Stulp, Gert

AU - van der Most, Peter J

AU - de Vlaming, Ronald

AU - Bakshi, Andrew

AU - Briley, Daniel A

AU - Rahal, Charles

AU - Hellpap, Robert

AU - Nyman, Anastasia

AU - Esko, Tõnu

AU - Metspalu, Andres

AU - Medland, Sarah E

AU - Martin, Nicholas G

AU - Barban, Nicola

AU - Snieder, Harold

AU - Robinson, Matthew R

AU - Mills, Melinda C

PY - 2017/10

Y1 - 2017/10

N2 - Meta-analyses of genome-wide association studies (GWAS), which dominate genetic discovery are based on data from diverse historical time periods and populations. Genetic scores derived from GWAS 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 from across compared to within populations. We show that the hidden heritability varies substantially: from zero (height), to 20% for BMI, 37% for education, 40% for age at first birth and up to 75% for number of children. Simulations demonstrate that our results more likely reflect heterogeneity in phenotypic measurement or gene-environment interaction 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.

AB - Meta-analyses of genome-wide association studies (GWAS), which dominate genetic discovery are based on data from diverse historical time periods and populations. Genetic scores derived from GWAS 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 from across compared to within populations. We show that the hidden heritability varies substantially: from zero (height), to 20% for BMI, 37% for education, 40% for age at first birth and up to 75% for number of children. Simulations demonstrate that our results more likely reflect heterogeneity in phenotypic measurement or gene-environment interaction 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.

KW - Journal Article

KW - BODY-MASS INDEX

KW - GENOME-WIDE ASSOCIATION

KW - COMMON SNPS EXPLAIN

KW - MISSING HERITABILITY

KW - HUMAN HEIGHT

KW - EDUCATIONAL-ATTAINMENT

KW - GENETIC-VARIATION

KW - COMPLEX DISEASES

KW - LARGE PROPORTION

KW - FERTILITY

U2 - 10.1038/s41562-017-0195-1

DO - 10.1038/s41562-017-0195-1

M3 - Article

C2 - 29051922

VL - 1

SP - 757

EP - 765

JO - Nature Human Behaviour

JF - Nature Human Behaviour

SN - 2397-3374

IS - 10

ER -

ID: 49322632