title: Candidate gene analysis of femoral neck trabecular and cortical volumetric bone mineral density in older men.
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.
authors.affiliation: Epidemiology, University of Pittsburgh, Pittsburgh, PA 15261, USA.
authors.forename: Laura M
authors.initials: LM
authors.lastname: Yerges
authors.forename: Lambertus
authors.initials: L
authors.lastname: Klei
authors.forename: Jane A
authors.initials: JA
authors.lastname: Cauley
authors.forename: Kathryn
authors.initials: K
authors.lastname: Roeder
authors.forename: Candace M
authors.initials: CM
authors.lastname: Kammerer
authors.forename: Kristine E
authors.initials: KE
authors.lastname: Ensrud
authors.forename: Cara S
authors.initials: CS
authors.lastname: Nestlerode
authors.forename: Cora
authors.initials: C
authors.lastname: Lewis
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Lang
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Barrett-Connor
authors.forename: Susan P
authors.initials: SP
authors.lastname: Moffett
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Hoffman
authors.forename: Robert E
authors.initials: RE
authors.lastname: Ferrell
authors.forename: Eric S
authors.initials: ES
authors.lastname: Orwoll
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Zmuda
mesh_terms: D015502:Absorptiometry, Photon; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D015519:Bone Density / Q000235:genetics*; D005272:Femur Neck / Q000033:anatomy & histology* / Q000000981:diagnostic imaging; D050723:Fractures, Bone / Q000000981:diagnostic imaging / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D014057:Tomography, X-Ray Computed