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A Bivariate Whole-Genome Linkage Scan Suggests Several Shared Genomic Regions for Obesity and Osteoporosis

Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education (Z.-H.T., S.-F.L., F.-Y.D., H.-Y.D., L.-J.T., H.-W.D.), College of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, People’s Republic of China; Osteoporosis Research Center and Department of Biomedical Sciences (P.X., L.-J.Z., H.-Y.D., D.-H.X., R.R.R., H.-W.D.), Creighton University Medical Center, Omaha, Nebraska 68131; and Departments of Orthopedic Surgery and Basic Medical Sciences (H.-Y.D., H.S., H.-W.D.), University of Missouri-Kansas City, Kansas City, Missouri 64108-2792

Address all correspondence and requests for reprints to: Hong-Wen Deng, Ph.D., Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri-Kansas City, 2411 Holmes Street, Room M3-C03, Kansas City, Missouri 64108-2792. E-mail: dengh{at}umkc.edu.

Context: A genome-wide bivariate analysis was conducted for body fat mass (BFM) and bone mineral density (BMD) in a large Caucasian sample. We found some quantitative trait loci shared by BFM and BMD in the total sample and the gender-specific subgroups, and quantitative trait loci with potential pleiotropy were disclosed. BFM and BMD, as the respective measure for obesity and osteoporosis, are phenotypically and genetically correlated. However, specific genomic regions accounting for their genetic correlation are unknown.

Objective: To identify systemically the shared genomic regions for BFM and BMD, we performed a bivariate whole-genome linkage scan in 4498 Caucasian individuals from 451 families for BFM and BMD at the hip, spine, and wrist, respectively. Linkage analyses were performed in the total sample and the male and female subgroups, respectively.

Results: In the entire sample, suggestive linkages were detected at 7p22-p21 (LOD 2.69) for BFM and spine BMD, 6q27 (LOD 2.30) for BFM and hip BMD, and 11q13 (LOD 2.64) for BFM and wrist BMD. Male-specific suggestive linkages were found at 13q12 (LOD 3.23) for BFM and spine BMD and at 7q21 (LOD 2.59) for BFM and hip BMD. Female-specific suggestive LOD scores were 3.32 at 15q13 for BFM and spine BMD and 3.15 at 6p25–24 for BFM and wrist BMD.

Conclusions: Several shared genomic regions for BFM and BMD were identified here. Our data may benefit further positional and functional studies, aimed at eventually uncovering the complex mechanism underlying the shared genetic determination of obesity and osteoporosis.