title: A genome-wide association analysis implicates SOX6 as a candidate gene for wrist bone mass.
abstract: Osteoporosis is a highly heritable common bone disease leading to fractures that severely impair the life quality of patients. Wrist fractures caused by osteoporosis are largely due to the scarcity of wrist bone mass. Here we report the results of a genome-wide association study (GWAS) of wrist bone mineral density (BMD). We examined ∼500000 SNP markers in 1000 unrelated homogeneous Caucasian subjects and found a novel allelic association with wrist BMD at rs11023787 in the SOX6 (SRY (sex determining region Y)-box 6) gene (P=9.00×10(-5)). Subjects carrying the C allele of rs11023787 in SOX6 had significantly higher mean wrist BMD values than those with the T allele (0.485:0.462 g cm(-2) for C allele vs. T allele carriers). For validation, we performed SOX6 association for BMD in an independent Chinese sample and found that SNP rs11023787 was significantly associated with wrist BMD in the Chinese sample (P=6.41×10(-3)). Meta-analyses of the GWAS scan and the replication studies yielded P-values of 5.20×10(-6) for rs11023787. Results of this study, together with the functional relevance of SOX6 in cartilage formation, support the SOX6 gene as an important gene for BMD variation.
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha 410081, China.
authors.forename: LiJun
authors.initials: L
authors.lastname: Tan
authors.forename: Rong
authors.initials: R
authors.lastname: Liu
authors.forename: ShuFeng
authors.initials: S
authors.lastname: Lei
authors.forename: Rong
authors.initials: R
authors.lastname: Pan
authors.forename: TieLin
authors.initials: T
authors.lastname: Yang
authors.forename: Han
authors.initials: H
authors.lastname: Yan
authors.forename: YuFang
authors.initials: Y
authors.lastname: Pei
authors.forename: Fang
authors.initials: F
authors.lastname: Yang
authors.forename: Feng
authors.initials: F
authors.lastname: Zhang
authors.forename: Feng
authors.initials: F
authors.lastname: Pan
authors.forename: YinPin
authors.initials: Y
authors.lastname: Zhang
authors.forename: HongGang
authors.initials: H
authors.lastname: Hu
authors.forename: Shawn
authors.initials: S
authors.lastname: Levy
authors.forename: HongWen
authors.initials: H
authors.lastname: Deng
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D044466:Asian People / Q000235:genetics; D015519:Bone Density / Q000235:genetics*; D005260:Female; D050723:Fractures, Bone / Q000209:etiology; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000150:complications / Q000473:pathology / Q000503:physiopathology; D020641:Polymorphism, Single Nucleotide; D055755:SOXD Transcription Factors / Q000235:genetics* / Q000378:metabolism; D014953:Wrist / Q000033:anatomy & histology* / Q000502:physiology
chemical_list: D005819:Genetic Markers; C486270:SOX6 protein, human; D055755:SOXD Transcription Factors