Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men

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

Research output: Contribution to journalArticle

34 Citations (Scopus)

Abstract

In contrast to conventional dual-energy X-ray absorptiometry, quantitative computed tomography separately measures trabecular and cortical volumetric bone mineral density (vBMD). Little is known about the genetic variants associated with trabecular and cortical vBMD in humans, although both may be important for determining bone strength and osteoporotic risk. In the current analysis, we tested the hypothesis that there are genetic variants associated with trabecular and cortical vBMD at the femoral neck by genotyping 4608 tagging and potentially functional single-nucleotide polymorphisms (SNPs) in 383 bone metabolism candidate genes in 822 Caucasian men aged 65 years or older from the Osteoporotic Fractures in Men Study (MrOS). Promising SNP associations then were tested for replication in an additional 1155 men from the same study. We identified SNPs in five genes (IFNAR2, NFATC1, SMAD1, HOXA, and KLF10) that were robustly associated with cortical vBMD and SNPs in nine genes (APC, ATF2, BMP3, BMP7, FGF18, FLT1, TGFB3, THRB, and RUNX1) that were robustly associated with trabecular vBMD. There was no overlap between genes associated with cortical vBMD and trabecular vBMD. These findings identify novel genetic variants for cortical and trabecular vBMD and raise the possibility that some genetic loci may be unique for each bone compartment.

Original languageEnglish (US)
Pages (from-to)330-338
Number of pages9
JournalJournal of Bone and Mineral Research
Volume25
Issue number2
DOIs
StatePublished - 2010

Fingerprint

Femur Neck
Genetic Association Studies
Bone Density
Single Nucleotide Polymorphism
Bone and Bones
Transforming Growth Factor beta3
APC Genes
Genes
Osteoporotic Fractures
Genetic Loci
Cortical Bone
Photon Absorptiometry
Tomography

Keywords

  • BMD
  • Genetics
  • Men
  • Osteoporosis
  • QCT

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)

Cite this

Yerges, L. M., Klei, L., Cauley, J. A., Roeder, K., Kammerer, C. M., Ensrud, K. E., ... Zmuda, J. M. (2010). Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men. Journal of Bone and Mineral Research, 25(2), 330-338. https://doi.org/10.1359/jbmr.090729

Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men. / Yerges, Laura M.; Klei, Lambertus; Cauley, Jane A.; Roeder, Kathryn; Kammerer, Candace M.; Ensrud, Kristine E.; Nestlerode, Cara S.; Lewis, Cora; Lang, Thomas F.; Barrett-Connor, Elizabeth; Moffett, Susan P.; Hoffman, Andrew R.; Ferrell, Robert E.; Orwoll, Eric; Zmuda, Joseph M.

In: Journal of Bone and Mineral Research, Vol. 25, No. 2, 2010, p. 330-338.

Research output: Contribution to journalArticle

Yerges, LM, Klei, L, Cauley, JA, Roeder, K, Kammerer, CM, Ensrud, KE, Nestlerode, CS, Lewis, C, Lang, TF, Barrett-Connor, E, Moffett, SP, Hoffman, AR, Ferrell, RE, Orwoll, E & Zmuda, JM 2010, 'Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men', Journal of Bone and Mineral Research, vol. 25, no. 2, pp. 330-338. https://doi.org/10.1359/jbmr.090729
Yerges, Laura M. ; Klei, Lambertus ; Cauley, Jane A. ; Roeder, Kathryn ; Kammerer, Candace M. ; Ensrud, Kristine E. ; Nestlerode, Cara S. ; Lewis, Cora ; Lang, Thomas F. ; Barrett-Connor, Elizabeth ; Moffett, Susan P. ; Hoffman, Andrew R. ; Ferrell, Robert E. ; Orwoll, Eric ; Zmuda, Joseph M. / Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men. In: Journal of Bone and Mineral Research. 2010 ; Vol. 25, No. 2. pp. 330-338.
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