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. 2015 Nov;47(11):1357-62.
doi: 10.1038/ng.3401. Epub 2015 Sep 14.

Population genetic differentiation of height and body mass index across Europe

Matthew R Robinson  1 , Gibran Hemani  1 , Carolina Medina-Gomez  2 , Massimo Mezzavilla  3   4 , Tonu Esko  5   6   7   8 , Konstantin Shakhbazov  1 , Joseph E Powell  1   9 , Anna Vinkhuyzen  1 , Sonja I Berndt  10 , Stefan Gustafsson  11 , Anne E Justice  12 , Bratati Kahali  13   14 , Adam E Locke  15 , Tune H Pers  6   7   8   16 , Sailaja Vedantam  6   7 , Andrew R Wood  17 , Wouter van Rheenen  18 , Ole A Andreassen  19 , Paolo Gasparini  3   4 , Andres Metspalu  5 , Leonard H van den Berg  18 , Jan H Veldink  18 , Fernando Rivadeneira  2 , Thomas M Werge  20   21   22 , Goncalo R Abecasis  15 , Dorret I Boomsma  23   24   25 , Daniel I Chasman  8   26 , Eco J C de Geus  23   24   25 , Timothy M Frayling  17 , Joel N Hirschhorn  5   6   7   8 , Jouke Jan Hottenga  23   24   25 , Erik Ingelsson  11   27 , Ruth J F Loos  28   29   30   31 , Patrik K E Magnusson  32 , Nicholas G Martin  33 , Grant W Montgomery  33 , Kari E North  13   14   34 , Nancy L Pedersen  32 , Timothy D Spector  35 , Elizabeth K Speliotes  15 , Michael E Goddard  36   37 , Jian Yang  1   9 , Peter M Visscher  1   9
Affiliations

Population genetic differentiation of height and body mass index across Europe

Matthew R Robinson et al. Nat Genet. 2015 Nov.

Abstract

Across-nation differences in the mean values for complex traits are common, but the reasons for these differences are unknown. Here we find that many independent loci contribute to population genetic differences in height and body mass index (BMI) in 9,416 individuals across 14 European countries. Using discovery data on over 250,000 individuals and unbiased effect size estimates from 17,500 sibling pairs, we estimate that 24% (95% credible interval (CI) = 9%, 41%) and 8% (95% CI = 4%, 16%) of the captured additive genetic variance for height and BMI, respectively, reflect population genetic differences. Population genetic divergence differed significantly from that in a null model (height, P < 3.94 × 10(-8); BMI, P < 5.95 × 10(-4)), and we find an among-population genetic correlation for tall and slender individuals (r = -0.80, 95% CI = -0.95, -0.60), consistent with correlated selection for both phenotypes. Observed differences in height among populations reflected the predicted genetic means (r = 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).

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Conflict of interest statement

The authors declare no conflicts of interest pertaining to this study.

Figures

Figure 1
Figure 1. Observed divergence and predicted genetic divergence in height and body mass index (BMI) and height across 14 European nations
Across Europe, the observed means and predicted genetic means for height and BMI of 14 European nations are shown. From recently published data, we estimated national differences in mean height and BMI for 14 European nations accounting for time trends (Figure 1), with a European average height of 171.1 (95% CI: 169.6, 172.8) and average BMI of 25.0 (95% CI: 24.7, 25.3) across nations for males between the years 2000 and 2010.
Figure 2
Figure 2. Predicted genetic differentiation compared to the expectation under drift for height and body mass index across 14 European nations
Mean predicted genetic (blue) and null model (grey) values of 14 European nations are shown, with 95% credible intervals, for (a) height (cm) and (b) body mass index (BMI units). ISO2 country codes indicate each nation. The average p-value of differentiation from the null expectation is p<4.3e−14 for height and p<8.7e−07 for BMI. (c) Pattern of population co-differentiation of height and body mass index across 14 European nations (blue). The negative population genetic co-differentiation of −0.80 (95% CI: −0.95, −0.60) is represented by a blue ellipse.
Figure 2
Figure 2. Predicted genetic differentiation compared to the expectation under drift for height and body mass index across 14 European nations
Mean predicted genetic (blue) and null model (grey) values of 14 European nations are shown, with 95% credible intervals, for (a) height (cm) and (b) body mass index (BMI units). ISO2 country codes indicate each nation. The average p-value of differentiation from the null expectation is p<4.3e−14 for height and p<8.7e−07 for BMI. (c) Pattern of population co-differentiation of height and body mass index across 14 European nations (blue). The negative population genetic co-differentiation of −0.80 (95% CI: −0.95, −0.60) is represented by a blue ellipse.
Figure 2
Figure 2. Predicted genetic differentiation compared to the expectation under drift for height and body mass index across 14 European nations
Mean predicted genetic (blue) and null model (grey) values of 14 European nations are shown, with 95% credible intervals, for (a) height (cm) and (b) body mass index (BMI units). ISO2 country codes indicate each nation. The average p-value of differentiation from the null expectation is p<4.3e−14 for height and p<8.7e−07 for BMI. (c) Pattern of population co-differentiation of height and body mass index across 14 European nations (blue). The negative population genetic co-differentiation of −0.80 (95% CI: −0.95, −0.60) is represented by a blue ellipse.
Figure 3
Figure 3. Association between observed population means and predicted genetic population means for height and body mass index across 14 European nations
Predicted population genetic means and observed population means for (a) height and (b) body mass index (BMI). P values give the significance of the multivariate Pearson product moment correlation between the predicted population genetic means and the observed population means for both traits. For height, the correlation (r = 0.51; 95% CI 0.39, 0.61) was greater than that expected under the null model (r = 0.03, 95% CI −0.21, 0.17). For BMI, the correlation (r = −0.10, 95% CI −0.19, 0.01) was not significantly different from the null expectation (r = −0.08, 95% CI −0.24, 0.15).
Figure 3
Figure 3. Association between observed population means and predicted genetic population means for height and body mass index across 14 European nations
Predicted population genetic means and observed population means for (a) height and (b) body mass index (BMI). P values give the significance of the multivariate Pearson product moment correlation between the predicted population genetic means and the observed population means for both traits. For height, the correlation (r = 0.51; 95% CI 0.39, 0.61) was greater than that expected under the null model (r = 0.03, 95% CI −0.21, 0.17). For BMI, the correlation (r = −0.10, 95% CI −0.19, 0.01) was not significantly different from the null expectation (r = −0.08, 95% CI −0.24, 0.15).
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