title: Genome-wide association study identified UQCC locus for spine bone size in humans.
abstract: Bone size (BS) contributes significantly to the risk of osteoporotic fracture. Osteoporotic spine fracture is one of the most disabling outcomes of osteoporosis. This study aims to identify genomic loci underlying spine BS variation in humans. We performed a genome-wide association scan in 2286 unrelated Caucasians using Affymetrix 6.0 SNP arrays. Areal BS (cm(2)) at lumbar spine was measured using dual energy X-ray absorptiometry scanners. SNPs of interest were subjected to replication analyses and meta-analyses with additional two independent Caucasian populations (N=1000 and 2503) and one Chinese population (N=1627). In the initial GWAS, 91 SNPs were associated with spine BS (P<1.0E-4). Eight contiguous SNPs were found clustering in a haplotype block within UQCC gene (ubiquinol-cytochrome creductase complex chaperone). Association of the above eight SNPs with spine BS was replicated in one Caucasian and one Chinese populations. Meta-analyses (N=7416) generated much stronger association signals for these SNPs (e.g., P=1.86E-07 for SNP rs6060373), supporting association of UQCC with spine BS across ethnicities. This study identified a novel locus, i.e., the UQCC gene, for spine BS variation in humans. Future functional studies will contribute to elucidating the mechanisms by which UQCC regulates bone growth and development.
authors.affiliation: Center of Genetic Epidemiology and Genomics, School of Public Health, Soochow University, Suzhou, Jiangsu 215123, PR China.
authors.forename: Fei-Yan
authors.initials: FY
authors.lastname: Deng
authors.forename: Shan-Shan
authors.initials: SS
authors.lastname: Dong
authors.forename: Xiang-Hong
authors.initials: XH
authors.lastname: Xu
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Liu
authors.forename: Yao-Zhong
authors.initials: YZ
authors.lastname: Liu
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Jian
authors.initials: J
authors.lastname: Li
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D055106:Genome-Wide Association Study; D006239:Haplotypes; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D013131:Spine / Q000033:anatomy & histology*
chemical_list: D008565:Membrane Proteins; C582875:UQCC1 protein, human