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 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

^*Corresponding author for this work

University of Queensland
Erasmus University Rotterdam
IRCCS Ospedale Infantile Burlo Garofolo - Trieste
Wellcome Trust
University of Tartu
Boston Children's Hospital
Broad Institute
Harvard University
National Institutes of Health
Uppsala University
University of North Carolina at Chapel Hill
University of Michigan, Ann Arbor
Technical University of Denmark
University of Exeter
Utrecht University
University of Oslo
MHC Sct. Hans
University of Copenhagen
iPSYCH
VU University Medical Center
Vrije Universiteit Amsterdam
Brigham and Women’s Hospital
University of Oxford
University of Cambridge
Icahn School of Medicine at Mount Sinai
Karolinska Institutet
Queensland Institute of Medical Research
St Thomas’ Hospital Campus
State Government of Victoria
University of Melbourne

Research output: Contribution to journal › Article › peer-review

149 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
Pages (from-to)	1357-1361
Number of pages	5
Journal	Nature Genetics
Volume	47
Issue number	11
DOIs	https://doi.org/10.1038/ng.3401
Publication status	Published - 1 Nov 2015
Externally published	Yes

Access to Document

10.1038/ng.3401

Cite this

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), 1357-1361. https://doi.org/10.1038/ng.3401

@article{1e0df7dc433b4ffe9f3a1f941c724150,

title = "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).",

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

note = "Publisher Copyright: {\textcopyright} 2015 Nature America, Inc.",

year = "2015",

month = nov,

day = "1",

doi = "10.1038/ng.3401",

language = "English",

volume = "47",

pages = "1357--1361",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "11",

}

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, Van Den Berg, LH, 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. 1357-1361. https://doi.org/10.1038/ng.3401

TY - JOUR

T1 - Population genetic differentiation of height and body mass index across Europe

AU - Robinson, Matthew R.

AU - Hemani, Gibran

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 - Van Den Berg, Leonard H.

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.

AU - Yang, Jian

AU - Visscher, Peter M.

PY - 2015/11/1

Y1 - 2015/11/1

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).

UR - https://www.scopus.com/pages/publications/84945484144

U2 - 10.1038/ng.3401

DO - 10.1038/ng.3401

M3 - Article

C2 - 26366552

AN - SCOPUS:84945484144

SN - 1061-4036

VL - 47

SP - 1357

EP - 1361

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -

Population genetic differentiation of height and body mass index across Europe

Abstract

Access to Document

Other files and links

Fingerprint

Cite this