Genome‐wide association study for femoral neck bone geometry |
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| Authors: | Lan‐Juan Zhao Xiao‐Gang Liu Yao‐Zhong Liu Yong‐Jun Liu Christopher J Papasian Bao‐Yong Sha Feng Pan Yan‐Fang Guo Liang Wang Han Yan Dong‐Hai Xiong Zi‐Hui Tang Tie‐Lin Yang Xiang‐Ding Chen Yan Guo Jian Li Hui Shen Feng Zhang Shu‐Feng Lei Robert R Recker Hong‐Wen Deng |
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| Affiliation: | 1. Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA;2. School of Medicine, University of Missouri–Kansas City, Kansas City, MO, USA;3. Key Laboratory of Biomedical Information Engineering, Ministry of Education and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shanxi 710049, Peoples Republic of China;4. Laboratory of Molecular and Statistical Genetics, College of Life Sciences Hunan Normal University, Changsha, Hunan 410081, Peoples Republic of China |
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| 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 × 10?7), an index of bone structural instability, and with femoral cortical thickness (CT, P = 1.9 × 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 × 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 × 10?3 for BR and P = 1.4 × 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 × 10?3) was found. Our observations suggest that RTP3 may be a novel candidate gene for femoral neck bone geometry. © 2010 American Society for Bone and Mineral Research |
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| Keywords: | genome‐wide association femoral neck bone geometry bone fracture RTP3 |
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