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. 2009 Dec;24(12):2039-49.
doi: 10.1359/jbmr.090524.

High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men

Laura M Yerges  1 , Lambertus Klei, Jane A Cauley, Kathryn Roeder, Candace M Kammerer, Susan P Moffett, Kristine E Ensrud, Cara S Nestlerode, Lynn M Marshall, Andrew R Hoffman, Cora Lewis, Thomas F Lang, Elizabeth Barrett-Connor, Robert E Ferrell, Eric S Orwoll, Joseph M Zmuda; MrOS Research Group
Affiliations

High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men

Laura M Yerges et al. J Bone Miner Res. 2009 Dec.

Abstract

Genetics is a well-established but poorly understood determinant of BMD. Whereas some genetic variants may influence BMD throughout the body, others may be skeletal site specific. We initially screened for associations between 4608 tagging and potentially functional single nucleotide polymorphisms (SNPs) in 383 candidate genes and femoral neck and lumbar spine volumetric BMD (vBMD) measured from QCT scans among 862 community-dwelling white men >or=65 yr of age in the Osteoporotic Fractures in Men Study (MrOS). The most promising SNP associations (p < 0.01) were validated by genotyping an additional 1156 white men from MrOS. This analysis identified 8 SNPs in 6 genes (APC, DMP1, FGFR2, FLT1, HOXA, and PTN) that were associated with femoral neck vBMD and 13 SNPs in 7 genes (APC, BMPR1B, FOXC2, HOXA, IGFBP2, NFATC1, and SOST) that were associated with lumbar spine vBMD in both genotyping samples (p < 0.05). Although most associations were specific to one skeletal site, SNPs in the APC and HOXA gene regions were associated with both femoral neck and lumbar spine BMD. This analysis identifies several novel and robust genetic associations for volumetric BMD, and these findings in combination with other data suggest the presence of genetic loci for volumetric BMD that are at least to some extent skeletal-site specific.

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Figures

FIG. 1
FIG. 1
SNP association results for femoral neck vBMD. Association results for the femoral neck are presented for the first phase of genotyping (discovery sample) in A and in the validation sample in B. Specifically, the –log of the p value observed is presented on the y-axis. The most significant result of the two models tested (either additive or recessive) is presented for each SNP. The SNPs are ordered across the x-axis by chromosome and the base pair position on the chromosome. Odd numbered chromosomes and the X chromosome are presented in light gray. Even numbered chromosomes are presented in dark gray. In A, the dark dashed line represents p = 0.015 and the dotted line represents p = 0.05. The dotted line in B represents p = 0.05, and SNPs with p ≤ 0.05 are labeled with the gene symbol that they lie in.
FIG. 2
FIG. 2
SNP association results for lumbar spine vBMD. Association results for the lumbar spine are presented for the discovery (A) and validation sample (B). Specifically, the –log of the p value observed is presented on the y-axis, and SNPs are ordered across the x-axis by chromosome and base pair position. The most significant result of the two models tested (either additive or recessive) is presented for each SNP. Odd numbered chromosomes and the X chromosome are presented in light gray. Even numbered chromosomes are presented in dark gray. In A, the dark dashed line represents p = 0.015 and the dotted line represents p = 0.05. The dotted line in B represents p = 0.05, and SNPs with p ≤ 0.05 are labeled with the gene symbol that they lie in.
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References

    1. Riggs BL, Melton LJ., III The worldwide problem of osteoporosis: Insights afforded by epidemiology. Bone. 1995;17(Suppl):505S–511S. - PubMed
    1. Silverman SL. Quality-of-life issues in osteoporosis. Curr Rheumatol Rep. 2005;7:39–45. - PubMed
    1. Anonymous. Osteoporosis prevention, diagnosis, and therapy. JAMA. 2001;285:785–795. - PubMed
    1. Ralston SH, de Crombrugghe B. Genetic regulation of bone mass and susceptibility to osteoporosis. Genes Dev. 2006;20:2492–2506. - PubMed
    1. Jones G, Nguyen TV. Associations between maternal peak bone mass and bone mass in prepubertal male and female children. J Bone Miner Res. 2000;15:1998–2004. - PubMed

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