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. and Mills, Melinda C. (2017) Hidden heritability due to heterogeneity across seven populations. Nature Human Behaviour, 1 10: 757-765. doi: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.
Title Hidden heritability due to heterogeneity across seven populations
Journal name Nature Human Behaviour   Check publisher's open access policy
ISSN 2397-3374
Publication date 2017-09-11
Year available 2017
Sub-type Article (original research)
DOI 10.1038/s41562-017-0195-1
Open Access Status DOI
Volume 1
Issue 10
Start page 757
End page 765
Total pages 9
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 3205 Experimental and Cognitive Psychology
3207 Social Psychology
2802 Behavioral Neuroscience
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.
Keyword age at first birth
educational attainment
gene-environment interaction
hidden heritability
human reproduction
missing heritability
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID HHSN268201100012C
RC4 AG039029
R01 AA007535
R01 AA014041
R01 MH066206
U01 AG009740
R01 AA013326
R56 DA012854
R01 DK075787
R01 AA013321
R01 DA012854
RC2 AG036495
R01 AA013320
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
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Created: Wed, 25 Oct 2017, 21:01:10 EST