Genome-wide association study for femoral neck bone geometry.
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.
Zhao
Lan-Juan
LJ
Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA.
Liu
Xiao-Gang
XG
Liu
Yao-Zhong
YZ
Liu
Yong-Jun
YJ
Papasian
Christopher J
CJ
Sha
Bao-Yong
BY
Pan
Feng
F
Guo
Yan-Fang
YF
Wang
Liang
L
Yan
Han
H
Xiong
Dong-Hai
DH
Tang
Zi-Hui
ZH
Yang
Tie-Lin
TL
Chen
Xiang-Ding
XD
Guo
Yan
Y
Li
Jian
J
Shen
Hui
H
Zhang
Feng
F
Lei
Shu-Feng
SF
Recker
Robert R
RR
Deng
Hong-Wen
HW
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
D026901:Membrane Transport Proteins