Genetic determination of osteoporosis: lessons learned from a large genome-wide linkage study.
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.
Xiong
Dong-Hai
DH
Key Laboratory of Biomedical Information Engineering, Ministry of Education, Xi'an Jiaotong University, Xi'an, P. R. China 710049.
Wang
Jin-Tang
JT
Wang
Wei
W
Guo
Yan-Fang
YF
Xiao
Peng
P
Shen
Hui
H
Jiang
Hui
H
Chen
Yuan
Y
Deng
Hongyi
H
Drees
Betty
B
Recker
Robert R
RR
Deng
Hong-Wen
HW
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