title: Genome-wide association study identifies ALDH7A1 as a novel susceptibility gene for osteoporosis.
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 = 2.08x10(-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 = 6.39x10(-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.
authors.affiliation: Key Laboratory of Biomedical Information Engineering of Ministry of Education, and Institute of Molecular Genetics, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, People's Republic of China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Guo
authors.forename: Li-Jun
authors.initials: LJ
authors.lastname: Tan
authors.forename: Shu-Feng
authors.initials: SF
authors.lastname: Lei
authors.forename: Tie-Lin
authors.initials: TL
authors.lastname: Yang
authors.forename: Xiang-Ding
authors.initials: XD
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.forename: Xiaogang
authors.initials: X
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Zhi-Xin
authors.initials: ZX
authors.lastname: Zhang
authors.forename: Qi
authors.initials: Q
authors.lastname: Zhou
authors.forename: Chuan
authors.initials: C
authors.lastname: Qiu
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Dong
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Xu
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Xue-Zhen
authors.initials: XZ
authors.lastname: Zhu
authors.forename: Shan-Lin
authors.initials: SL
authors.lastname: Liu
authors.forename: Xiang-Li
authors.initials: XL
authors.lastname: Wang
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Yi
authors.initials: Y
authors.lastname: Luo
authors.forename: Li-Shu
authors.initials: LS
authors.lastname: Zhang
authors.forename: Meng
authors.initials: M
authors.lastname: Li
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Wang
authors.forename: Ting
authors.initials: T
authors.lastname: Wen
authors.forename: Betty
authors.initials: B
authors.lastname: Drees
authors.forename: James
authors.initials: J
authors.lastname: Hamilton
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Papasian
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Song
authors.forename: Jing
authors.initials: J
authors.lastname: Cheng
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000368:Aged; D000444:Aldehyde Dehydrogenase / Q000235:genetics*; D044466:Asian People / Q000235:genetics; D015519:Bone Density; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics* / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: C089507:ALDH7A1 protein, human; D000444:Aldehyde Dehydrogenase