Genome-wide association study for femoral neck bone geometry

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 & 1 others Hong Wen Deng

Research output: Contribution to journalArticle

27 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)320-329
Number of pages10
JournalJournal of Bone and Mineral Research
Volume25
Issue number2
DOIs
StatePublished - 2010

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Genome-Wide Association Study
Femur Neck
Hip Fractures
Bone and Bones
Proteins
Single Nucleotide Polymorphism
Pedigree
Thigh
Femur
Genes

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism
  • Orthopedics and Sports Medicine
  • Medicine(all)

Cite this

Zhao, L. J., Liu, X. G., Liu, Y. Z., Liu, Y. J., Papasian, C. J., Sha, B. Y., ... Deng, H. W. (2010). Genome-wide association study for femoral neck bone geometry. Journal of Bone and Mineral Research, 25(2), 320-329. https://doi.org/10.1359/jbmr.090726

Genome-wide association study for femoral neck bone geometry. / Zhao, Lan Juan; Liu, Xiao Gang; Liu, Yao Zhong; Liu, Yong Jun; Papasian, Christopher J.; Sha, Bao Yong; Pan, Feng; Guo, Yan Fang; Wang, Liang; Yan, Han; Xiong, Dong Hai; Tang, Zi Hui; Yang, Tie Lin; Chen, Xiang Ding; Guo, Yan; Li, Jian; Shen, Hui; Zhang, Feng; Lei, Shu Feng; Recker, Robert R.; Deng, Hong Wen.

In: Journal of Bone and Mineral Research, Vol. 25, No. 2, 2010, p. 320-329.

Research output: Contribution to journalArticle

Zhao, LJ, Liu, XG, Liu, YZ, Liu, YJ, Papasian, CJ, Sha, BY, Pan, F, Guo, YF, Wang, L, Yan, H, Xiong, DH, Tang, ZH, Yang, TL, Chen, XD, Guo, Y, Li, J, Shen, H, Zhang, F, Lei, SF, Recker, RR & Deng, HW 2010, 'Genome-wide association study for femoral neck bone geometry', Journal of Bone and Mineral Research, vol. 25, no. 2, pp. 320-329. https://doi.org/10.1359/jbmr.090726
Zhao, Lan Juan ; Liu, Xiao Gang ; Liu, Yao Zhong ; Liu, Yong Jun ; Papasian, Christopher J. ; Sha, Bao Yong ; Pan, Feng ; Guo, Yan Fang ; Wang, Liang ; Yan, Han ; Xiong, Dong Hai ; Tang, Zi Hui ; Yang, Tie Lin ; Chen, Xiang Ding ; Guo, Yan ; Li, Jian ; Shen, Hui ; Zhang, Feng ; Lei, Shu Feng ; Recker, Robert R. ; Deng, Hong Wen. / Genome-wide association study for femoral neck bone geometry. In: Journal of Bone and Mineral Research. 2010 ; Vol. 25, No. 2. pp. 320-329.
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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.",
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AU - Sha, Bao Yong

AU - Pan, Feng

AU - Guo, Yan Fang

AU - Wang, Liang

AU - Yan, Han

AU - Xiong, Dong Hai

AU - Tang, Zi Hui

AU - Yang, Tie Lin

AU - Chen, Xiang Ding

AU - Guo, Yan

AU - Li, Jian

AU - Shen, Hui

AU - Zhang, Feng

AU - Lei, Shu Feng

AU - Recker, Robert R.

AU - Deng, Hong Wen

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N2 - 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.

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