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; Hong Wen Deng

doi:10.1359/jbmr.090726

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. ReckerHong Wen Deng

Research output: Contribution to journal › Article › peer-review

35 Scopus citations

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 language	English (US)
Pages (from-to)	320-329
Number of pages	10
Journal	Journal of Bone and Mineral Research
Volume	25
Issue number	2
DOIs	https://doi.org/10.1359/jbmr.090726
State	Published - Feb 2010

Keywords

Bone fracture
Femoral neck bone geometry
Genome-wide association
RTP3

ASJC Scopus subject areas

Endocrinology, Diabetes and Metabolism
Orthopedics and Sports Medicine

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Zhao, L. J., Liu, X. G., Liu, Y. Z., Liu, Y. J., Papasian, C. J., Sha, B. Y., Pan, F., Guo, Y. F., Wang, L., Yan, H., Xiong, D. H., Tang, Z. H., Yang, T. L., Chen, X. D., Guo, Y., Li, J., Shen, H., Zhang, F., Lei, S. F., ... 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

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

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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 × 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.",

keywords = "Bone fracture, Femoral neck bone geometry, Genome-wide association, RTP3",

author = "Zhao, {Lan Juan} and Liu, {Xiao Gang} and Liu, {Yao Zhong} and Liu, {Yong Jun} and Papasian, {Christopher J.} and Sha, {Bao Yong} and Feng Pan and Guo, {Yan Fang} and Liang Wang and Han Yan and Xiong, {Dong Hai} and Tang, {Zi Hui} and Yang, {Tie Lin} and Chen, {Xiang Ding} and Yan Guo and Jian Li and Hui Shen and Feng Zhang and Lei, {Shu Feng} and Recker, {Robert R.} and Deng, {Hong Wen}",

year = "2010",

month = feb,

doi = "10.1359/jbmr.090726",

language = "English (US)",

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AU - Zhao, Lan Juan

AU - Liu, Xiao Gang

AU - Liu, Yao Zhong

AU - Liu, Yong Jun

AU - Papasian, Christopher J.

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

PY - 2010/2

Y1 - 2010/2

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.

AB - 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.

KW - Bone fracture

KW - Femoral neck bone geometry

KW - Genome-wide association

KW - RTP3

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JO - Journal of Bone and Mineral Research

JF - Journal of Bone and Mineral Research

IS - 2

ER -

Genome-wide association study for femoral neck bone geometry

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