Population genetic differentiation of height and body mass index across Europe

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).

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. 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. 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. 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. 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. 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).