title: Genetic determination of osteoporosis: lessons learned from a large genome-wide linkage study.
abstract: Osteoporosis is a common disease with strong genetic control. We performed an autosomal linkage scan in a large pedigree-based sample of 4,498 subjects for a composite osteoporosis phenotype that combines osteoporotic fracture (OF) and low bone mineral density (BMD). All of the subjects were U.S. Caucasians recruited in the Omaha area of Nebraska. Sex-specific linkage analyses and autosomal imprinting analyses were also conducted. For conventional linkage analyses in the total sample, we identified suggestive linkage on chromosomes 14q32 (LOD = 2.61), 7p14 (LOD = 2.42), and 11q25 (LOD = 2.09). In female subjects a significant linkage signal was detected on chromosome 14q22 (LOD = 3.53) and another two peaks were detected on chromosomes 7p14 (LOD = 3.07) and 9p21 (LOD = 2.29). Suggestive evidence of imprinted loci was found with paternally derived alleles on chromosomes 1q42 (LOD = 2.12) and 9q34 (LOD = 1.88). Some evidence of linkage to maternally derived alleles was found on chromosome 7q22 (LOD = 1.67). Our study provides new clues to osteoporosis genetic research and for the first time suggests that genomic imprinting effects may play a role in the etiology of osteoporosis.
authors.affiliation: Key Laboratory of Biomedical Information Engineering, Ministry of Education, Xi'an Jiaotong University, Xi'an, P. R. China 710049.
authors.forename: Dong-Hai
authors.initials: DH
authors.lastname: Xiong
authors.forename: Jin-Tang
authors.initials: JT
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Wang
authors.forename: Yan-Fang
authors.initials: YF
authors.lastname: Guo
authors.forename: Peng
authors.initials: P
authors.lastname: Xiao
authors.forename: Hui
authors.initials: H
authors.lastname: Shen
authors.forename: Hui
authors.initials: H
authors.lastname: Jiang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Chen
authors.forename: Hongyi
authors.initials: H
authors.lastname: Deng
authors.forename: Betty
authors.initials: B
authors.lastname: Drees
authors.forename: Robert R
authors.initials: RR
authors.lastname: Recker
authors.forename: Hong-Wen
authors.initials: HW
authors.lastname: Deng
mesh_terms: D015519:Bone Density; D005260:Female; D008040:Genetic Linkage / Q000235:genetics*; D005828:Genetics, Population / Q000379:methods; D018392:Genomic Imprinting / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D010641:Phenotype; D014481:United States