title: Genome-wide association study for femoral neck bone geometry.
abstract: Poor femoral neck bone geometry at the femur is an important risk factor for hip fracture. We conducted a genome-wide association study (GWAS) of femoral neck bone geometry, examining approximately 379,000 eligible single-nucleotide polymorphisms (SNPs) in 1000 Caucasians. A common genetic variant, rs7430431 in the receptor transporting protein 3 (RTP3) gene, was identified in strong association with the buckling ratio (BR, P = 1.6 x 10(-7)), an index of bone structural instability, and with femoral cortical thickness (CT, P = 1.9 x 10(-6)). The RTP3 gene is located in 3p21.31, a region that we found to be linked with CT (LOD = 2.19, P = 6.0 x 10(-4)) in 3998 individuals from 434 pedigrees. The replication analyses in 1488 independent Caucasians and 2118 Chinese confirmed the association of rs7430431 to BR and CT (combined P = 7.0 x 10(-3) for BR and P = 1.4 x 10(-2) for CT). In addition, 350 hip fracture patients and 350 healthy control individuals were genotyped to assess the association of the RTP3 gene with the risk of hip fracture. Significant association between a nearby common SNP, rs10514713 of the RTP3 gene, and hip fracture (P = 1.0 x 10(-3)) was found. Our observations suggest that RTP3 may be a novel candidate gene for femoral neck bone geometry.
authors.affiliation: Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA.
authors.forename: Lan-Juan
authors.initials: LJ
authors.lastname: Zhao
authors.forename: Xiao-Gang
authors.initials: XG
authors.lastname: Liu
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.forename: Bao-Yong
authors.initials: BY
authors.lastname: Sha
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Liang
authors.initials: L
authors.lastname: Wang
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Xiong
authors.forename: Zi-Hui
authors.initials: ZH
authors.lastname: Tang
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Xiang-Ding
authors.initials: XD
authors.lastname: Chen
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Lei
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D000368:Aged; D044466:Asian People; D005260:Female; D005272:Femur Neck / Q000033:anatomy & histology*; D055106:Genome-Wide Association Study; D006620:Hip Fractures / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics; D008875:Middle Aged; D011110:Polymorphism, Genetic; D044465:White People
chemical_list: D026901:Membrane Transport Proteins