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

2017-10

<p>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.</p>

Nature Human Behaviour, 1(10), p. 757-765

2397-3374

29051922

https://hdl.handle.net/1959.11/53132

Nature Publishing Group

Hidden heritability due to heterogeneity across seven populations

Journal Article

Publication