@article{10.1371/journal.pgen.1000806, doi = {10.1371/journal.pgen.1000806}, author = {Guo, Yan AND Tan, Li-Jun AND Lei, Shu-Feng AND Yang, Tie-Lin AND Chen, Xiang-Ding AND Zhang, Feng AND Chen, Yuan AND Pan, Feng AND Yan, Han AND Liu, Xiaogang AND Tian, Qing AND Zhang, Zhi-Xin AND Zhou, Qi AND Qiu, Chuan AND Dong, Shan-Shan AND Xu, Xiang-Hong AND Guo, Yan-Fang AND Zhu, Xue-Zhen AND Liu, Shan-Lin AND Wang, Xiang-Li AND Li, Xi AND Luo, Yi AND Zhang, Li-Shu AND Li, Meng AND Wang, Jin-Tang AND Wen, Ting AND Drees, Betty AND Hamilton, James AND Papasian, Christopher J. AND Recker, Robert R. AND Song, Xiao-Ping AND Cheng, Jing AND Deng, Hong-Wen}, journal = {PLOS Genetics}, publisher = {Public Library of Science}, title = {Genome-Wide Association Study Identifies ALDH7A1 as a Novel Susceptibility Gene for Osteoporosis}, year = {2010}, month = {01}, volume = {6}, url = {https://doi.org/10.1371/journal.pgen.1000806}, pages = {1-8}, abstract = {Osteoporosis is a major public health problem. It is mainly characterized by low bone mineral density (BMD) and/or low-trauma osteoporotic fractures (OF), both of which have strong genetic determination. The specific genes influencing these phenotypic traits, however, are largely unknown. Using the Affymetrix 500K array set, we performed a case-control genome-wide association study (GWAS) in 700 elderly Chinese Han subjects (350 with hip OF and 350 healthy matched controls). A follow-up replication study was conducted to validate our major GWAS findings in an independent Chinese sample containing 390 cases with hip OF and 516 controls. We found that a SNP, rs13182402 within the ALDH7A1 gene on chromosome 5q31, was strongly associated with OF with evidence combined GWAS and replication studies (P = 2.08×10−9, odds ratio = 2.25). In order to explore the target risk factors and potential mechanism underlying hip OF risk, we further examined this candidate SNP's relevance to hip BMD both in Chinese and Caucasian populations involving 9,962 additional subjects. This SNP was confirmed as consistently associated with hip BMD even across ethnic boundaries, in both Chinese and Caucasians (combined P = 6.39×10−6), further attesting to its potential effect on osteoporosis. ALDH7A1 degrades and detoxifies acetaldehyde, which inhibits osteoblast proliferation and results in decreased bone formation. Our findings may provide new insights into the pathogenesis of osteoporosis.}, number = {1}, }