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 language | English |
|---|---|
| Pages (from-to) | 2961-2972 |
| Number of pages | 12 |
| Journal | Molecular Biology and Evolution |
| Volume | 32 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 1 2015 |
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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 journal › Article
}
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 -