Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men |
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| Authors: | 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 S Orwoll Joseph M Zmuda |
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| Affiliation: | 1. Epidemiology, University of Pittsburgh, Pittsburgh, PA, USA;2. Psychiatry, University of Pittsburgh, Pittsburgh, PA, USA;3. Statistics, Carnegie Mellon University, Pittsburgh, PA, USA;4. Genetics, University of Pittsburgh, Pittsburgh, PA, USA;5. Medicine, University of Minnesota, Minneapolis, MN, USA;6. University of Alabama at Birmingham, Birmingham, AL, USA;7. Radiology, University of California–San Francisco, San Francisco, CA, USA;8. Department of Family and Preventive Medicine, University of California–San Diego, La Jolla, CA, USA;9. Veterans Affairs, Palo Alto Health Care System and Stanford University, Palo Alto, CA, USA;10. Medicine, Oregon Health & Science University, Portland, OR, USA |
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| 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. © 2010 American Society for Bone and Mineral Research |
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| Keywords: | osteoporosis Genetics BMD men qCT |
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