OPG and RANK Polymorphisms Are Both Associated with Cortical Bone Mineral Density: Findings from a Metaanalysis of the Avon Longitudinal Study of Parents and Children and Gothenburg Osteoporosis and Obesity Determinants Cohorts
Copyright policy )OPG and RANK Polymorphisms Are Both Associated with Cortical Bone Mineral Density: Findings from a Metaanalysis of the Avon Longitudinal Study of Parents and Children and Gothenburg Osteoporosis and Obesity Determinants Cohorts
Several single-nucleotide polymorphisms (SNPs) have been reliably associated with areal bone mineral density (aBMD) in genome-wide association studies of mostly older subjects.We aimed to test those SNPs for an association with peripheral quantitative computed tomography (pQCT) bone measures in two young cohorts.We genotyped nine SNPs from the most promising aBMD candidates in a cohort of 15-yr-olds [in the Avon Longitudinal Study of Parents and Children (ALSPAC)] and carried out association analysis with several tibial pQCT measures to determine whether these candidates were important during adolescent growth and which particular skeletal parameters each of the candidates were acting upon. We also carried out a metaanalysis of the SNPs for association with cortical bone mineral density (BMDC) in ALSPAC and a similar male-only study (Gothenburg Osteoporosis and Obesity Determinants).In the ALSPAC cohort, we found a significant association between RANK SNP (rs3018362) and BMDC but not any of the other pQCT bone measures. In the metaanalysis, we found the OPG SNP (rs4355801) and the RANK SNP (rs3018362) to be significantly associated with BMDC. We also found suggestive evidence of an association between the MARK3 SNP (rs2010281) and BMDC but with a direction of effect opposite to that previously reported.The association of genes from the RANK/RANKL/OPG pathway and BMDC provides new insight into how this system might affect the skeleton, confirming it to be associated with volumetric cortical bone density but observing no relationship with bone size.
- University of Queensland Australia
- University of Bristol United Kingdom
- University of Queensland Australia
Adult, Male, Adolescent, Genotype, Receptor Activator of Nuclear Factor-kappa B, Patient Selection, Osteoprotegerin, Polymorphism, Single Nucleotide, 618, Endocrinology & Metabolism, Bone Density, 616, Humans, Osteoporosis, Original Article, Female, Longitudinal Studies, Obesity, Child, Genetic Association Studies
Adult, Male, Adolescent, Genotype, Receptor Activator of Nuclear Factor-kappa B, Patient Selection, Osteoprotegerin, Polymorphism, Single Nucleotide, 618, Endocrinology & Metabolism, Bone Density, 616, Humans, Osteoporosis, Original Article, Female, Longitudinal Studies, Obesity, Child, Genetic Association Studies
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