High-density association study of 383 candidate genes for volumetric BMD at the femoral neck and lumbar spine among older men.
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.
Yerges
Laura M
LM
Department of Epidemiology, University of Pittsburgh, Pittsburgh, Pennsylvania 15261, USA.
Klei
Lambertus
L
Cauley
Jane A
JA
Roeder
Kathryn
K
Kammerer
Candace M
CM
Moffett
Susan P
SP
Ensrud
Kristine E
KE
Nestlerode
Cara S
CS
Marshall
Lynn M
LM
Hoffman
Andrew R
AR
Lewis
Cora
C
Lang
Thomas F
TF
Barrett-Connor
Elizabeth
E
Ferrell
Robert E
RE
Orwoll
Eric S
ES
Zmuda
Joseph M
JM
D015519:Bone Density / Q000235:genetics*; D005269:Femur; D020869:Gene Expression Profiling; D055106:Genome-Wide Association Study; D006801:Humans; D008159:Lumbar Vertebrae; D008297:Male; D020641:Polymorphism, Single Nucleotide