Population genetic differentiation of height and body mass index across Europe

MR Robinson; G Hemani; C Medina-Gomez; M Mezzavilla; T Esko-; K Shakhbazov; JE Powell; A Vinkhuyzen; SI Berndt; S Gustafsson; AE Justice; B Kahali; AE Locke; TH Pers; S Vedantam; AR Wood; W van Rheenen; OA Andreassen; P Gasparini; A Metspalu; LH van den Berg; JH Veldink; Fernando Rivadeneira; TM Werge; GR Abecasis; DI Boomsma; DI Chasman; EJC de Geus; TM Frayling; JN Hirschhorn; JJ (Jouke Jan) Hottenga; E Ingelsson; RJF Loos; PKE Magnusson; NG Martin; GW Montgomery; KE North; NL Pedersen; TD Spector; EK Speliotes; ME Goddard; Jiaqi Yang; PM Visscher

doi:10.1038/ng.3401

Population genetic differentiation of height and body mass index across Europe

MR Robinson, G Hemani, C Medina-Gomez, M Mezzavilla, T Esko-, K Shakhbazov, JE Powell, A Vinkhuyzen, SI Berndt, S Gustafsson, AE Justice, B Kahali, AE Locke, TH Pers, S Vedantam, AR Wood, W van Rheenen, OA Andreassen, P Gasparini, A MetspaluLH van den Berg, JH Veldink, Fernando Rivadeneira, TM Werge, GR Abecasis, DI Boomsma, DI Chasman, EJC de Geus, TM Frayling, JN Hirschhorn, JJ (Jouke Jan) Hottenga, E Ingelsson, RJF Loos, PKE Magnusson, NG Martin, GW Montgomery, KE North, NL Pedersen, TD Spector, EK Speliotes, ME Goddard, Jiaqi Yang, PM Visscher

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

145 Citations (Scopus)

Abstract

Across-nation differences in the mean values for complex traits are common(1-8), 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 x 10(-8); BMI, P < 5.95 x 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	Undefined/Unknown
Pages (from-to)	1357-+
Journal	Nature Genetics
Volume	47
Issue number	11
DOIs	https://doi.org/10.1038/ng.3401
Publication status	Published - 2015

Research programs

EMC MM-01-39-09-A

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10.1038/ng.3401

Cite this

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., ... Visscher, PM. (2015). Population genetic differentiation of height and body mass index across Europe. Nature Genetics, 47(11), 1357-+. https://doi.org/10.1038/ng.3401

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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(1-8), 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 x 10(-8); BMI, P < 5.95 x 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 = "MR Robinson and G Hemani and C Medina-Gomez and M Mezzavilla and T Esko- and K Shakhbazov and JE Powell and A Vinkhuyzen and SI Berndt and S Gustafsson and AE Justice and B Kahali and AE Locke and TH Pers and S Vedantam and AR Wood and {van Rheenen}, W and OA Andreassen and P Gasparini and A Metspalu and {van den Berg}, LH and JH Veldink and Fernando Rivadeneira and TM Werge and GR Abecasis and DI Boomsma and DI Chasman and {de Geus}, EJC and TM Frayling and JN Hirschhorn and Hottenga, {JJ (Jouke Jan)} and E Ingelsson and RJF Loos and PKE Magnusson and NG Martin and GW Montgomery and KE North and NL Pedersen and TD Spector and EK Speliotes and ME Goddard and Jiaqi Yang and PM Visscher",

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doi = "10.1038/ng.3401",

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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-+. https://doi.org/10.1038/ng.3401

TY - JOUR

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

AU - Robinson, MR

AU - Hemani, G

AU - Medina-Gomez, C

AU - Mezzavilla, M

AU - Esko-, T

AU - Shakhbazov, K

AU - Powell, JE

AU - Vinkhuyzen, A

AU - Berndt, SI

AU - Gustafsson, S

AU - Justice, AE

AU - Kahali, B

AU - Locke, AE

AU - Pers, TH

AU - Vedantam, S

AU - Wood, AR

AU - van Rheenen, W

AU - Andreassen, OA

AU - Gasparini, P

AU - Metspalu, A

AU - van den Berg, LH

AU - Veldink, JH

AU - Rivadeneira, Fernando

AU - Werge, TM

AU - Abecasis, GR

AU - Boomsma, DI

AU - Chasman, DI

AU - de Geus, EJC

AU - Frayling, TM

AU - Hirschhorn, JN

AU - Hottenga, JJ (Jouke Jan)

AU - Ingelsson, E

AU - Loos, RJF

AU - Magnusson, PKE

AU - Martin, NG

AU - Montgomery, GW

AU - North, KE

AU - Pedersen, NL

AU - Spector, TD

AU - Speliotes, EK

AU - Goddard, ME

AU - Yang, Jiaqi

AU - Visscher, PM

PY - 2015

Y1 - 2015

N2 - Across-nation differences in the mean values for complex traits are common(1-8), 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 x 10(-8); BMI, P < 5.95 x 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(1-8), 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 x 10(-8); BMI, P < 5.95 x 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).

U2 - 10.1038/ng.3401

DO - 10.1038/ng.3401

M3 - Article

C2 - 26366552

SN - 1061-4036

VL - 47

SP - 1357-+

JO - Nature Genetics

JF - Nature Genetics

IS - 11

ER -