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

Laura M. Yerges, 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

Research output: Contribution to journalArticle

49 Scopus citations

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 ≥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.

Original languageEnglish (US)
Pages (from-to)2039-2049
Number of pages11
JournalJournal of Bone and Mineral Research
Volume24
Issue number12
DOIs
StatePublished - Dec 1 2009

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Keywords

  • BMD
  • Genetics
  • Men
  • Osteoporosis
  • QCT

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine

Cite this

Yerges, L. M., Klei, L., Cauley, J. A., Roeder, K., Kammerer, C. M., Moffett, S. P., Ensrud, K. E., Nestlerode, C. S., Marshall, L. M., Hoffman, A. R., Lewis, C., Lang, T. F., Barrett-Connor, E., Ferrell, R. E., Orwoll, E. S., & Zmuda, J. M. (2009). High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men. Journal of Bone and Mineral Research, 24(12), 2039-2049. https://doi.org/10.1359/jbmr.090524