BMD Loci Contribute to Ethnic and Developmental Differences in Skeletal Fragility across Populations: Assessment of Evolutionary Selection Pressures. Medina-Gómez, C.; Chesi, A.; Heppe, D. H. M.; Zemel, B. S.; Yin, J.; Kalkwarf, H. J.; Hofman, A.; Lappe, J. M.; Kelly, A.; Kayser, M.; Oberfield, S. E.; Gilsanz, V.; Uitterlinden, A. G.; Shepherd, J. A.; Jaddoe, V. W. V.; Grant, S. F. A.; Lao, O.; and Rivadeneira, F. Molecular Biology and Evolution, 32(11):2961–2972, November, 2015.
doi  abstract   bibtex   
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.
@article{medina-gomez_bmd_2015,
	title = {{BMD} {Loci} {Contribute} to {Ethnic} and {Developmental} {Differences} in {Skeletal} {Fragility} across {Populations}: {Assessment} of {Evolutionary} {Selection} {Pressures}},
	volume = {32},
	issn = {1537-1719},
	shorttitle = {{BMD} {Loci} {Contribute} to {Ethnic} and {Developmental} {Differences} in {Skeletal} {Fragility} across {Populations}},
	doi = {10.1093/molbev/msv170},
	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.},
	language = {eng},
	number = {11},
	journal = {Molecular Biology and Evolution},
	author = {Medina-Gómez, Carolina and Chesi, Alessandra and Heppe, Denise H. M. and Zemel, Babette S. and Yin, Jia-Lian and Kalkwarf, Heidi J. and Hofman, Albert and Lappe, Joan M. and Kelly, Andrea and Kayser, Manfred and Oberfield, Sharon E. and Gilsanz, Vicente and Uitterlinden, André G. and Shepherd, John A. and Jaddoe, Vincent W. V. and Grant, Struan F. A. and Lao, Oscar and Rivadeneira, Fernando},
	month = nov,
	year = {2015},
	pmid = {26226985},
	pmcid = {PMC4651235},
	keywords = {Adult, African Continental Ancestry Group, Alleles, Asian Continental Ancestry Group, Biological Evolution, Bone Density, Child, Continental Population Groups, European Continental Ancestry Group, Evolution, Molecular, Female, Genetic Association Studies, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Osteoporosis, Polymorphism, Single Nucleotide, Selection, Genetic, adaptation, bone mineral density, ethnic differences, genome-wide association studies, polygenic, selective pressures},
	pages = {2961--2972}
}
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