Evidence for major pleiotropic effects on bone size variation from a principal component analysis of 451 Caucasian families1
Li-jun TAN
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China
Search for more papers by this authorYao-zhong LIU
Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri, Kansas City, Missouri 64108-2792, USA
Search for more papers by this authorPeng XIAO
Osteoporosis Research Center, Creighton University Medical Center Omaha, Nebraska 68131, USA
Search for more papers by this authorFang YANG
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China
Search for more papers by this authorZi-hui TANG
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China
Search for more papers by this authorPeng-yuan LIU
Osteoporosis Research Center, Creighton University Medical Center Omaha, Nebraska 68131, USA
Search for more papers by this authorRobert R RECKER
Osteoporosis Research Center, Creighton University Medical Center Omaha, Nebraska 68131, USA
Search for more papers by this authorCorresponding Author
Hong-wen DENG
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China
Institute of Molecular Genetics and the Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiao Tong University, Xi'an 710049, China
Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri, Kansas City, Missouri 64108-2792, USA
Correspondence to Prof Hong-wen DENG. Phn/Fax 86-731-887-2791. E-mail [email protected]Search for more papers by this authorLi-jun TAN
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China
Search for more papers by this authorYao-zhong LIU
Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri, Kansas City, Missouri 64108-2792, USA
Search for more papers by this authorPeng XIAO
Osteoporosis Research Center, Creighton University Medical Center Omaha, Nebraska 68131, USA
Search for more papers by this authorFang YANG
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China
Search for more papers by this authorZi-hui TANG
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China
Search for more papers by this authorPeng-yuan LIU
Osteoporosis Research Center, Creighton University Medical Center Omaha, Nebraska 68131, USA
Search for more papers by this authorRobert R RECKER
Osteoporosis Research Center, Creighton University Medical Center Omaha, Nebraska 68131, USA
Search for more papers by this authorCorresponding Author
Hong-wen DENG
Laboratory of Molecular and Statistical Genetics and the Key Laboratory of Protein Chemistry and Developmental Biology of Ministry of Education, Hunan Normal University, Changsha 410081, China
Institute of Molecular Genetics and the Key Laboratory of Biomedical Information Engineering of Ministry of Education, Xi'an Jiao Tong University, Xi'an 710049, China
Departments of Orthopedic Surgery and Basic Medical Sciences, University of Missouri, Kansas City, Missouri 64108-2792, USA
Correspondence to Prof Hong-wen DENG. Phn/Fax 86-731-887-2791. E-mail [email protected]Search for more papers by this authorThe study was partially supported by grants from NIH (K01 AR02 170-01, R01 AR45349-01, and R01 GM60402-01 A1), and also benefited from grants from the National Science Foundation of China (No 30230210, 30470534, and 30600364) and a Scientific Research Fund of Hunan Provincial Education Department (No 05B037).
Abstract
Aim: To identify pleiotropic quantitative trait loci (QTL) influencing bone size (BS) at different skeletal sites in Caucasians. Methods: In a sample containing 3899 Caucasians from 451 pedigrees, 410 microsatellite markers spaced ∼8.9 cM apart across the human genome were genotyped. Phenotypical and genetic correlations of BS at lumbar spine, hip (femoral neck, trochanter, and intertrochanter regions), and wrist (ultradistal, mid-distal, and one-third distal sites) were determined using bivariate quantitative genetic analysis. A principal component analysis (PCA) was performed to obtain principal component (PC) factors that were then subjected to variance components linkage analysis to identify regions linked to the PC. Results: Genetic correlations of BS at different skeletal sites ranged fr om 0.40 to 0.7 9 (P<0.001). The PCA yielded a PC named PCtotal, which explained up to 76% of the total (co)variation of all the BS at the 7 skeletal sites for the whole sample. We identified a QTL influencing the BS of multiple skeletal sites on chromosome 7 at 140 cM [logarithm of odds (LOD)=2.85] in the overall sample. Sex-specific evidence for linkage was observed on chromosome 11 at 53 cM (LOD =2.82) in the male-only data subset. Conclusion: Our study identified several genomic regions that may have pleiotropic effects on different skeletal sites. These regions may contain genes that play a critical role in overall bone development and osteoporosis at multiple skeletal sites, hence are biologically and clinically important.
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