Population genetic differentiation of height and body mass index across Europe

Robinson, Matthew R., Hemani, Gibran, Medina-Gomez, Carolina, Mezzavilla, Massimo, Esko, Tonu, Shakhbazov, Konstantin, Powell, Joseph E., Vinkhuyzen, Anna, Berndt, Sonja I., Gustafsson, Stefan, Justice, Anne E., Kahali, Bratati, Locke, Adam E., Pers, Tune H., Vedantam, Sailaja, Wood, Andrew R., van Rheenen, Wouter, Andreassen, Ole A., Gasparini, Paolo, Metspalu, Andres, van den Berg, Leonard H., Veldink, Jan H., Rivadeneira, Fernando, Werge, Thomas M., Abecasis, Goncalo R., Boomsma, Dorret I., Chasman, Daniel I., de Geus, Eco J. C., Frayling, Timothy M., Hirschhorn, Joel N., Hottenga, Jouke Jan, Ingelsson, Erik, Loos, Ruth J. F., Magnusson, Patrik K. E., Martin, Nicholas G., Montgomery, Grant W., North, Kari E., Pedersen, Nancy L., Spector, Timothy D., Speliotes, Elizabeth K., Goddard, Michael E., Yang, Jian and Visscher, Peter M. (2015) Population genetic differentiation of height and body mass index across Europe. Nature Genetics, 47 11: 1357-1361. doi:10.1038/ng.3401


Author Robinson, Matthew R.
Hemani, Gibran
Medina-Gomez, Carolina
Mezzavilla, Massimo
Esko, Tonu
Shakhbazov, Konstantin
Powell, Joseph E.
Vinkhuyzen, Anna
Berndt, Sonja I.
Gustafsson, Stefan
Justice, Anne E.
Kahali, Bratati
Locke, Adam E.
Pers, Tune H.
Vedantam, Sailaja
Wood, Andrew R.
van Rheenen, Wouter
Andreassen, Ole A.
Gasparini, Paolo
Metspalu, Andres
van den Berg, Leonard H.
Veldink, Jan H.
Rivadeneira, Fernando
Werge, Thomas M.
Abecasis, Goncalo R.
Boomsma, Dorret I.
Chasman, Daniel I.
de Geus, Eco J. C.
Frayling, Timothy M.
Hirschhorn, Joel N.
Hottenga, Jouke Jan
Ingelsson, Erik
Loos, Ruth J. F.
Magnusson, Patrik K. E.
Martin, Nicholas G.
Montgomery, Grant W.
North, Kari E.
Pedersen, Nancy L.
Spector, Timothy D.
Speliotes, Elizabeth K.
Goddard, Michael E.
Yang, Jian
Visscher, Peter M.
Title Population genetic differentiation of height and body mass index across Europe
Journal name Nature Genetics   Check publisher's open access policy
ISSN 1546-1718
1061-4036
Publication date 2015-09-14
Year available 2015
Sub-type Article (original research)
DOI 10.1038/ng.3401
Open Access Status Not Open Access
Volume 47
Issue 11
Start page 1357
End page 1361
Total pages 8
Place of publication New York, NY, United States
Publisher Nature Publishing Group
Language eng
Subject 1311 Genetics
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).
Formatted abstract
Across-nation differences in the mean values for complex traits are common1, 2, 3, 4, 5, 6, 7, 8, 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 (= 0.51; P < 0.001), but environmental differences across Europe masked genetic differentiation for BMI (P < 0.58).
Keyword Estimating F-Statistics
Natural-Selection
Noncommunicable Diseases
Systematic Analysis
Global Variation
Complex Traits
Human Genome
Common Snps
Burden
Mortality
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 1078037
DE130100691
1052684
M-2005-1112
EU/QLRT-2001-01254
DK U01-066134
20070481
904-61-090
2008.024
184.021.007
EU/QLRT-2001-01254
HEALTH-F4-2007-201413
230374
U24-MH068457-06
R01-D0042157-01A
N01-HC-25195
N02-HL-64278
241944
U01-AG09740
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Queensland Brain Institute Publications
Official 2016 Collection
UQ Diamantina Institute Publications
 
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