title: Tests of linkage and association of the COL1A2 gene with bone phenotypes' variation in Chinese nuclear families.
abstract: In the present study, we simultaneously test linkage and/or association of the collagen type I alpha 2 (COL1A2) gene with bone mineral density (BMD) and bone area. A total of 1280 subjects from 407 Chinese nuclear families (including both parents and their daughters) were genotyped for an intragenic marker MspI in the COL1A2 gene. BMD and bone area at the lumbar spine and hip were measured by dual-energy X-ray absorptiometry. Applying the QTDT (quantitative transmission disequilibrium test) program, we performed tests for population stratification, within-family association (via transmission disequilibrium test), total association, linkage, and linkage while modeling association. Significant or marginal within-family associations were found with BMD at the lumbar spine (P = 0.013), trochanter (P = 0.004), and total hip (P = 0.053) and with bone area at the intertrochanteric region (P = 0.024) and total hip (P = 0.048). The positive associations were confirmed in permutations except for bone area at total hip (P > 0.10). A small proportion (<1%) of the population variance of bone phenotypes can be explained by the MspI polymorphism; however, it may be underestimated given the significant population stratification detected in our sample. Due to the limited number of sib pairs in this sample, we did not find evidence of linkage. In summary, the MspI polymorphism is likely to be in linkage disequilibrium with a nearby functional mutation affecting BMD and bone area.
authors.affiliation: Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, People's Republic of China. deng@creighton.edu
authors.forename: F Y
authors.initials: FY
authors.lastname: Deng
authors.forename: M Y
authors.initials: MY
authors.lastname: Liu
authors.forename: M X
authors.initials: MX
authors.lastname: Li
authors.forename: S F
authors.initials: SF
authors.lastname: Lei
authors.forename: Y J
authors.initials: YJ
authors.lastname: Qin
authors.forename: Q
authors.initials: Q
authors.lastname: Zhou
authors.forename: Y J
authors.initials: YJ
authors.lastname: Liu
authors.forename: H W
authors.initials: HW
authors.lastname: Deng
mesh_terms: D000328:Adult; D001483:Base Sequence; D015519:Bone Density / Q000187:drug effects*; D001842:Bone and Bones / Q000033:anatomy & histology*; D002681:China; D003094:Collagen / Q000235:genetics*; D024042:Collagen Type I; D004247:DNA / Q000235:genetics; D019003:Deoxyribonuclease HpaII; D005260:Female; D008040:Genetic Linkage; D014644:Genetic Variation; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D009679:Nuclear Family; D010641:Phenotype
chemical_list: D024042:Collagen Type I; D003094:Collagen; D004247:DNA; D019003:Deoxyribonuclease HpaII