title: Are bone mineral density loci  associated with hip osteoporotic fractures? A validation study on previously  reported genome-wide association loci in a Chinese population.
abstract: Osteoporosis  is a heritable disease characterized mainly by low bone mineral density (BMD)  and/or osteoporotic fractures (OF). Most genome-wide association studies on  osteoporosis have focused on BMD, whereas little effort has been expended to  identify genetic variants directly linked to OF. To determine whether BMD-loci  are also associated with OF risk, we performed a validation study to examine 23  BMD-loci reported by recent genome-wide association studies for association  with hip OF risk. Our sample consisted of 700 elderly Chinese Han subjects, 350  with hip OF and 350 healthy matched controls. We identified four BMD-loci that  were significantly associated with hip OF in this Chinese population, including  7q21 (FLJ42280, P = 1.17 × 10(-4) for rs4729260; P =  0.008 for rs7781370), 6p21 (MHC, P = 0.004 for rs3130340), 13q14 (TNFSF11,  P = 0.012 for rs9533090; P = 0.018 for rs9594759; P = 0.020 for rs9594738; P =  0.044 for rs9594751), and 18q21 (TNFRSF11A, P = 0.015 for rs884205). The  SNP rs4729260 at 7q21 remained significantly associated, even after  conservative Bonferroni's correction. Our results further highlight the  importance of these loci in the pathogenesis of osteoporosis, and demonstrate  that it is feasible and useful to use OF as the direct phenotype to conduct  genetic studies, to enhance our understanding of the genetic architecture of  osteoporosis.
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Ministry of Education, Department of Orthopaedics, School of Medicine, School of Life Science and Technology, The First Affiliated Hospital, Xi'an Jiaotong University, Xi'an, PR China.
authors.forename: Y
authors.initials: Y
authors.lastname: Guo
authors.forename: J-T
authors.initials: JT
authors.lastname: Wang
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Li
authors.forename: T-L
authors.initials: TL
authors.lastname: Yang
authors.forename: X-W
authors.initials: XW
authors.lastname: Zhang
authors.forename: Y-Z
authors.initials: YZ
authors.lastname: Liu
authors.forename: Q
authors.initials: Q
authors.lastname: Tian
authors.forename: H-W
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000368:Aged; D044466:Asian People / Q000235:genetics; D015519:Bone Density / Q000235:genetics*; D002681:China / Q000453:epidemiology; D002875:Chromosomes / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006615:Hip / Q000473:pathology; D006620:Hip Fractures / Q000235:genetics*; D006621:Hip Joint / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D058866:Osteoporotic Fractures / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide