Population genetic differentiation of height and body mass index across Europe

Matthew R Robinson; Gibran Hemani; Carolina Medina-Gomez; Massimo Mezzavilla; Tonu Esko; Konstantin Shakhbazov; Joseph E Powell; Anna Vinkhuyzen; Sonja I Berndt; Stefan Gustafsson; Anne E Justice; Bratati Kahali; Adam E Locke; Tune H Pers; Sailaja Vedantam; Andrew R Wood; Wouter van Rheenen; Ole A Andreassen; Paolo Gasparini; Andres Metspalu; Leonard H van den Berg; Jan H Veldink; Fernando Rivadeneira; Thomas M Werge; Goncalo R Abecasis; Dorret I Boomsma; Daniel I Chasman; Eco J C de Geus; Timothy M Frayling; Joel N Hirschhorn; Jouke Jan Hottenga; Erik Ingelsson; Ruth J F Loos; Patrik K E Magnusson; Nicholas G Martin; Grant W Montgomery; Kari E North; Nancy L Pedersen; Timothy D Spector; Elizabeth K Speliotes; Michael E Goddard; Jian Yang; Peter M Visscher

doi:10.1038/ng.3401

Population genetic differentiation of height and body mass index across Europe

Matthew R Robinson, Gibran Hemani, Carolina Medina-Gomez, Massimo Mezzavilla, Tonu Esko, Konstantin Shakhbazov, Joseph E Powell, Anna Vinkhuyzen, Sonja I Berndt, Stefan Gustafsson, Anne E Justice, Bratati Kahali, Adam E Locke, Tune H Pers, Sailaja Vedantam, Andrew R Wood, Wouter van Rheenen, Ole A Andreassen, Paolo Gasparini, Andres MetspaluLeonard H van den Berg, Jan H Veldink, Fernando Rivadeneira, Thomas M Werge, Goncalo R Abecasis, Dorret I Boomsma, Daniel I Chasman, Eco J C de Geus, Timothy M Frayling, Joel N Hirschhorn, Jouke Jan Hottenga, Erik Ingelsson, Ruth J F Loos, Patrik K E Magnusson, Nicholas G Martin, Grant W Montgomery, Kari E North, Nancy L Pedersen, Timothy D Spector, Elizabeth K Speliotes, Michael E Goddard, Jian Yang, Peter M Visscher

Department of Clinical Medicine

98 Citations (Scopus)

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).

Original language	English
Journal	Nature Genetics
Volume	47
Issue number	11
Pages (from-to)	1357-62, 2 unpag. Methods
Number of pages	8
ISSN	1061-4036
DOIs	https://doi.org/10.1038/ng.3401
Publication status	Published - 1 Nov 2015

Keywords

Algorithms
Body Height
Body Mass Index
Europe
Gene Expression Profiling
Gene-Environment Interaction
Genetic Variation
Genetics, Population
Genome-Wide Association Study
Genotype
Geography
Humans
Models, Genetic
Phenotype
Polymorphism, Single Nucleotide
Principal Component Analysis

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Robinson, M. R., Hemani, G., Medina-Gomez, C., Mezzavilla, M., Esko, T., Shakhbazov, K., Powell, J. E., Vinkhuyzen, A., Berndt, S. I., Gustafsson, S., Justice, A. E., Kahali, B., Locke, A. E., Pers, T. H., Vedantam, S., Wood, A. R., van Rheenen, W., Andreassen, O. A., Gasparini, P., ... Visscher, P. M. (2015). Population genetic differentiation of height and body mass index across Europe. Nature Genetics, 47(11), 1357-62, 2 unpag. Methods. https://doi.org/10.1038/ng.3401

Robinson, MR, Hemani, G, Medina-Gomez, C, Mezzavilla, M, Esko, T, Shakhbazov, K, Powell, JE, Vinkhuyzen, A, Berndt, SI, Gustafsson, S, Justice, AE, Kahali, B, Locke, AE, Pers, TH, Vedantam, S, Wood, AR, van Rheenen, W, Andreassen, OA, Gasparini, P, Metspalu, A, Berg, LHVD, Veldink, JH, Rivadeneira, F, Werge, TM, Abecasis, GR, Boomsma, DI, Chasman, DI, de Geus, EJC, Frayling, TM, Hirschhorn, JN, Hottenga, JJ, Ingelsson, E, Loos, RJF, Magnusson, PKE, Martin, NG, Montgomery, GW, North, KE, Pedersen, NL, Spector, TD, Speliotes, EK, Goddard, ME, Yang, J & Visscher, PM 2015, 'Population genetic differentiation of height and body mass index across Europe', Nature Genetics, vol. 47, no. 11, pp. 1357-62, 2 unpag. Methods. https://doi.org/10.1038/ng.3401

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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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AU - Medina-Gomez, Carolina

AU - Mezzavilla, Massimo

AU - Esko, Tonu

AU - Shakhbazov, Konstantin

AU - Powell, Joseph E

AU - Vinkhuyzen, Anna

AU - Berndt, Sonja I

AU - Gustafsson, Stefan

AU - Justice, Anne E

AU - Kahali, Bratati

AU - Locke, Adam E

AU - Pers, Tune H

AU - Vedantam, Sailaja

AU - Wood, Andrew R

AU - van Rheenen, Wouter

AU - Andreassen, Ole A

AU - Gasparini, Paolo

AU - Metspalu, Andres

AU - Berg, Leonard H van den

AU - Veldink, Jan H

AU - Rivadeneira, Fernando

AU - Werge, Thomas M

AU - Abecasis, Goncalo R

AU - Boomsma, Dorret I

AU - Chasman, Daniel I

AU - de Geus, Eco J C

AU - Frayling, Timothy M

AU - Hirschhorn, Joel N

AU - Hottenga, Jouke Jan

AU - Ingelsson, Erik

AU - Loos, Ruth J F

AU - Magnusson, Patrik K E

AU - Martin, Nicholas G

AU - Montgomery, Grant W

AU - North, Kari E

AU - Pedersen, Nancy L

AU - Spector, Timothy D

AU - Speliotes, Elizabeth K

AU - Goddard, Michael E

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AU - Visscher, Peter M

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N2 - 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).

AB - 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).

KW - Algorithms

KW - Body Height

KW - Body Mass Index

KW - Europe

KW - Gene Expression Profiling

KW - Gene-Environment Interaction

KW - Genetic Variation

KW - Genetics, Population

KW - Genome-Wide Association Study

KW - Genotype

KW - Geography

KW - Humans

KW - Models, Genetic

KW - Phenotype

KW - Polymorphism, Single Nucleotide

KW - Principal Component Analysis

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DO - 10.1038/ng.3401

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SN - 1061-4036

VL - 47

SP - 1357-62, 2 unpag. Methods

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Population genetic differentiation of height and body mass index across Europe

Abstract

Keywords

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