BMD loci contribute to ethnic and developmental differences in skeletal fragility across populations: Assessment of evolutionary selection pressures

Carolina Medina-Gómez, Alessandra Chesi, Denise H M Heppe, Babette S. Zemel, Jia Lian Yin, Heidi J. Kalkwarf, Albert Hofman, Joan M. Lappe, Andrea Kelly, Manfred Kayser, Sharon E. Oberfield, Vicente Gilsanz, André G. Uitterlinden, John A. Shepherd, Vincent W V Jaddoe, Struan F A Grant, Oscar Lao, Fernando Rivadeneira

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait.

Original languageEnglish
Pages (from-to)2961-2972
Number of pages12
JournalMolecular Biology and Evolution
Volume32
Issue number11
DOIs
StatePublished - Nov 1 2015

Fingerprint

bone density
Bone Density
bone
Pressure
loci
mineral
Population
osteoporosis
Osteoporosis
ancestry
ethnic differences
selection pressure
Gene Frequency
gene frequency
allele
bones
Pediatrics
Bone and Bones

All Science Journal Classification (ASJC) codes

  • Genetics
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics

Cite this

BMD loci contribute to ethnic and developmental differences in skeletal fragility across populations : Assessment of evolutionary selection pressures. / Medina-Gómez, Carolina; Chesi, Alessandra; Heppe, Denise H M; Zemel, Babette S.; Yin, Jia Lian; Kalkwarf, Heidi J.; Hofman, Albert; Lappe, Joan M.; Kelly, Andrea; Kayser, Manfred; Oberfield, Sharon E.; Gilsanz, Vicente; Uitterlinden, André G.; Shepherd, John A.; Jaddoe, Vincent W V; Grant, Struan F A; Lao, Oscar; Rivadeneira, Fernando.

In: Molecular Biology and Evolution, Vol. 32, No. 11, 01.11.2015, p. 2961-2972.

Research output: Contribution to journalArticle

Medina-Gómez, C, Chesi, A, Heppe, DHM, Zemel, BS, Yin, JL, Kalkwarf, HJ, Hofman, A, Lappe, JM, Kelly, A, Kayser, M, Oberfield, SE, Gilsanz, V, Uitterlinden, AG, Shepherd, JA, Jaddoe, VWV, Grant, SFA, Lao, O & Rivadeneira, F 2015, 'BMD loci contribute to ethnic and developmental differences in skeletal fragility across populations: Assessment of evolutionary selection pressures', Molecular Biology and Evolution, vol. 32, no. 11, pp. 2961-2972. https://doi.org/10.1093/molbev/msv170
Medina-Gómez, Carolina ; Chesi, Alessandra ; Heppe, Denise H M ; Zemel, Babette S. ; Yin, Jia Lian ; Kalkwarf, Heidi J. ; Hofman, Albert ; Lappe, Joan M. ; Kelly, Andrea ; Kayser, Manfred ; Oberfield, Sharon E. ; Gilsanz, Vicente ; Uitterlinden, André G. ; Shepherd, John A. ; Jaddoe, Vincent W V ; Grant, Struan F A ; Lao, Oscar ; Rivadeneira, Fernando. / BMD loci contribute to ethnic and developmental differences in skeletal fragility across populations : Assessment of evolutionary selection pressures. In: Molecular Biology and Evolution. 2015 ; Vol. 32, No. 11. pp. 2961-2972.
@article{b22aa054b190420ea7ea14a04690c540,
title = "BMD loci contribute to ethnic and developmental differences in skeletal fragility across populations: Assessment of evolutionary selection pressures",
abstract = "Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait.",
author = "Carolina Medina-G{\'o}mez and Alessandra Chesi and Heppe, {Denise H M} and Zemel, {Babette S.} and Yin, {Jia Lian} and Kalkwarf, {Heidi J.} and Albert Hofman and Lappe, {Joan M.} and Andrea Kelly and Manfred Kayser and Oberfield, {Sharon E.} and Vicente Gilsanz and Uitterlinden, {Andr{\'e} G.} and Shepherd, {John A.} and Jaddoe, {Vincent W V} and Grant, {Struan F A} and Oscar Lao and Fernando Rivadeneira",
year = "2015",
month = "11",
day = "1",
doi = "10.1093/molbev/msv170",
language = "English",
volume = "32",
pages = "2961--2972",
journal = "Molecular Biology and Evolution",
issn = "0737-4038",
publisher = "Oxford University Press",
number = "11",

}

TY - JOUR

T1 - BMD loci contribute to ethnic and developmental differences in skeletal fragility across populations

T2 - Assessment of evolutionary selection pressures

AU - Medina-Gómez, Carolina

AU - Chesi, Alessandra

AU - Heppe, Denise H M

AU - Zemel, Babette S.

AU - Yin, Jia Lian

AU - Kalkwarf, Heidi J.

AU - Hofman, Albert

AU - Lappe, Joan M.

AU - Kelly, Andrea

AU - Kayser, Manfred

AU - Oberfield, Sharon E.

AU - Gilsanz, Vicente

AU - Uitterlinden, André G.

AU - Shepherd, John A.

AU - Jaddoe, Vincent W V

AU - Grant, Struan F A

AU - Lao, Oscar

AU - Rivadeneira, Fernando

PY - 2015/11/1

Y1 - 2015/11/1

N2 - Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait.

AB - Bone mineral density (BMD) is a highly heritable trait used both for the diagnosis of osteoporosis in adults and to assess bone health in children. Ethnic differences in BMD have been documented, with markedly higher levels in individuals of African descent, which partially explain disparity in osteoporosis risk across populations. To date, 63 independent genetic variants have been associated with BMD in adults of Northern-European ancestry. Here, we demonstrate that at least 61 of these variants are predictive of BMD early in life by studying their compound effect within two multiethnic pediatric cohorts. Furthermore, we show that within these cohorts and across populations worldwide the frequency of those alleles associated with increased BMD is systematically elevated in individuals of Sub-Saharan African ancestry. The amount of differentiation in the BMD genetic scores among Sub-Saharan and non-Sub-Saharan populations together with neutrality tests, suggest that these allelic differences are compatible with the hypothesis of selective pressures acting on the genetic determinants of BMD. These findings constitute an explorative contribution to the role of selection on ethnic BMD differences and likely a new example of polygenic adaptation acting on a human trait.

UR - http://www.scopus.com/inward/record.url?scp=84946118373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84946118373&partnerID=8YFLogxK

U2 - 10.1093/molbev/msv170

DO - 10.1093/molbev/msv170

M3 - Article

C2 - 26226985

AN - SCOPUS:84946118373

VL - 32

SP - 2961

EP - 2972

JO - Molecular Biology and Evolution

JF - Molecular Biology and Evolution

SN - 0737-4038

IS - 11

ER -