Article :: Genomewide association study for femoral neck bone geometry

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Original Article

Genome-wide association study for femoral neck bone geometry

Lan-Juan Zhao^{1 4}, Xiao-Gang Liu³, Yao-Zhong Liu⁴, Yong-Jun Liu⁴, Christopher J Papasian⁴, Bao-Yong Sha^{1 2}, Feng Pan³, Yan-Fang Guo³, Liang Wang³, Han Yan³, Dong-Hai Xiong⁴, Zi-Hui Tang², Tie-Lin Yang³, Xiang-Ding Chen², Yan Guo³, Jian Li⁴, Hui Shen⁴, Feng Zhang³, Shu-Feng Lei^{2 4}, Robert R Recker¹, Hong-Wen Deng^{2 3 4 *}

¹Osteoporosis Research Center, Creighton University Medical Center, Omaha, NE, USA
²Laboratory of Molecular and Statistical Genetics, College of Life Sciences Hunan Normal University, Changsha, Hunan 410081, Peoples Republic of China
³Key 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
⁴School of Medicine, University of Missouri-Kansas City, Kansas City, MO, USA

email: Hong-Wen Deng (dengh@umkc.edu)

^*Correspondence to Hong-Wen Deng, Departments of Basic Medical Science and Orthopedic Surgery, University of Missouri-Kansas City, 2411 Holmes Street, Room M3-C03, Kansas City, MO 64108, USA.

Keywords

genome-wide association femoral neck bone geometry bone fracture RTP3

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

Received: 14 October 2008; Revised: 8 May 2009; Accepted: 8 July 2009

Digital Object Identifier (DOI)

10.1359/jbmr.090726 About DOI