Multi-stage genome-wide association meta-analyses identified two new loci for bone mineral density

Zhang, Lei, Choi, Hyung Jin, Estrada, Karol, Leo, Paul J., Li, Jian, Pei, Yu-Fang, Zhang, Yinping, Lin, Yong, Shen, Hui, Liu, Yao-Zhong, Liu, Yongjun, Zhao, Yingchun, Zhang, Ji-Gang, Tian, Qing, Wang, Yu-ping, Han, Yingying, Ran, Shu, Hai, Rong, Zhu, Xue-Zhen, Wu, Shuyan, Yan, Han, Liu, Xiaogang, Yang, Tie-Lin, Guo, Yan, Zhang, Feng, Guo, Yan-fang, Chen, Yuan, Chen, Xiangding, Tan, Lijun, Zhang, Lishu, Deng, Fei-Yan, Deng, Hongyi, Rivadeneira, Fernando, Duncan, Emma L., Lee, Jong Young, Han, Bok Ghee, Cho, Nam H., Nicholson, Geoffrey C., McColskey, Eugene, Eastell, Richard, Prince, Richard L., Eisman, John A., Jones, Graeme, Reid, Ian R., Sambrook, Philip N., Dennison, Elaine M., Danoy, Patrick, Yerges-Armstrong, Laura M., Streeten, Elizabeth A., Hu, Tian, Xiang, Shuanglin, Papasian, Christopher J., Brown, Matthew A., Shin, Chan Soo, Uitterlinden, André G. and Deng, Hong-Wen (2014) Multi-stage genome-wide association meta-analyses identified two new loci for bone mineral density. Human Molecular Genetics, 23 7: 1923-1933. doi:10.1093/hmg/ddt575

Author Zhang, Lei
Choi, Hyung Jin
Estrada, Karol
Leo, Paul J.
Li, Jian
Pei, Yu-Fang
Zhang, Yinping
Lin, Yong
Shen, Hui
Liu, Yao-Zhong
Liu, Yongjun
Zhao, Yingchun
Zhang, Ji-Gang
Tian, Qing
Wang, Yu-ping
Han, Yingying
Ran, Shu
Hai, Rong
Zhu, Xue-Zhen
Wu, Shuyan
Yan, Han
Liu, Xiaogang
Yang, Tie-Lin
Guo, Yan
Zhang, Feng
Guo, Yan-fang
Chen, Yuan
Chen, Xiangding
Tan, Lijun
Zhang, Lishu
Deng, Fei-Yan
Deng, Hongyi
Rivadeneira, Fernando
Duncan, Emma L.
Lee, Jong Young
Han, Bok Ghee
Cho, Nam H.
Nicholson, Geoffrey C.
McColskey, Eugene
Eastell, Richard
Prince, Richard L.
Eisman, John A.
Jones, Graeme
Reid, Ian R.
Sambrook, Philip N.
Dennison, Elaine M.
Danoy, Patrick
Yerges-Armstrong, Laura M.
Streeten, Elizabeth A.
Hu, Tian
Xiang, Shuanglin
Papasian, Christopher J.
Brown, Matthew A.
Shin, Chan Soo
Uitterlinden, André G.
Deng, Hong-Wen
Title Multi-stage genome-wide association meta-analyses identified two new loci for bone mineral density
Journal name Human Molecular Genetics   Check publisher's open access policy
ISSN 0964-6906
Publication date 2014-04-01
Year available 2013
Sub-type Article (original research)
DOI 10.1093/hmg/ddt575
Open Access Status Not Open Access
Volume 23
Issue 7
Start page 1923
End page 1933
Total pages 11
Place of publication Oxford, United Kingdom
Publisher Oxford University Press
Language eng
Formatted abstract
Aiming to identify novel genetic variants and to confirm previously identified genetic variants associated with bone mineral density (BMD), we conducted a three-stage genome-wide association (GWA) meta-analysis in 27 061 study subjects. Stage 1 meta-analyzed seven GWA samples and 11 140 subjects for BMDs at the lumbar spine, hip and femoral neck, followed by a Stage 2 in silico replication of 33 SNPs in 9258 subjects, and by a Stage 3 de novo validation of three SNPs in 6663 subjects. Combining evidence from all the stages, we have identified two novel loci that have not been reported previously at the genome-wide significance (GWS; 5.0 × 10−8) level: 14q24.2 (rs227425, P-value 3.98 × 10−13, SMOC1) in the combined sample of males and females and 21q22.13 (rs170183, P-value 4.15 × 10−9, CLDN14) in the female-specific sample. The two newly identified SNPs were also significant in the GEnetic Factors for OSteoporosis consortium (GEFOS, n = 32 960) summary results. We have also independently confirmed 13 previously reported loci at the GWS level: 1p36.12 (ZBTB40), 1p31.3 (GPR177), 4p16.3 (FGFRL1), 4q22.1 (MEPE), 5q14.3 (MEF2C), 6q25.1 (C6orf97, ESR1), 7q21.3 (FLJ42280, SHFM1), 7q31.31 (FAM3C, WNT16), 8q24.12 (TNFRSF11B), 11p15.3 (SOX6), 11q13.4 (LRP5), 13q14.11 (AKAP11) and 16q24 (FOXL1). Gene expression analysis in osteogenic cells implied potential functional association of the two candidate genes (SMOC1 and CLDN14) in bone metabolism. Our findings independently confirm previously identified biological pathways underlying bone metabolism and contribute to the discovery of novel pathways, thus providing valuable insights into the intervention and treatment of osteoporosis.
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes First published online: November 17, 2013

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
UQ Diamantina Institute Publications
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Created: Sat, 15 Mar 2014, 00:28:05 EST by Kylie Hengst on behalf of UQ Diamantina Institute