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Physiol. Genomics (March 23, 2004). doi:10.1152/physiolgenomics.00161.2002
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Submitted on November 19, 2002
Accepted on March 21, 2004

Genome Scan for QTLs Underlying Bone Size Variation at Ten Refined Skeletal Sites:Genetic Heterogeneity and the Significance of Phenotype Refinement

Qing-Yang Huang1, Fu-Hua Xu2, Hui Shen2, Hong-Yi Deng3, Theresa Conway1, Yong-Jun Liu2, Yao-Zhong Liu2, Jin-Long Li4, Miao-Xin Li5, K. Michael Davies1, Robert R Recker1, and Hong-Wen Deng6*

1 Osteoporosis Research Center, Creighton University, Omaha, NE, USA
2 Osteoporosis Research Center, Creighton University, Omaha, NE, USA; Department of Biomedical Sciences, Creighton University, Omaha, NE, USA
3 Department of Biomedical Sciences, Creighton University, Omaha, NE, USA; Center for Medical Informatics, School of Medicine, Yale University, New Haven, CT, USA
4 Center for Medical Informatics, School of Medicine, Yale University, New Haven, CT, USA
5 Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, ChangSha, Hunan, China
6 Osteoporosis Research Center, Creighton University, Omaha, NE, USA; Department of Biomedical Sciences, Creighton University, Omaha, NE, USA; Laboratory of Molecular and Statistical Genetics, College of Life Sciences, Hunan Normal University, ChangSha, Hunan, China

* To whom correspondence should be addressed. E-mail: deng{at}creighton.edu.

To identify quantitative trait loci (QTLs) underlying variation in bone size, we conducted a whole-genome linkage scan in 53 pedigrees with 630 subjects using 380 microsatellite markers. Lumbar area 1, 2, 3 and 4 at the spine, femoral neck, trochanter, intertrochanter areas at the hip, ultradistal, mid-distal, and one-third distal areas at the wrist, were measured by dual energy X-ray absorptiometry (DXA), and adjusted for age, height, weight, and sex. Two-point and multi-point linkage analyses were performed for skeletal bone size at each site and their composite measurements using the SOLAR package. Two chromosomal regions (1q22 and 10q21) were identified with significant evidence of linkage (LOD>4.32) to one-third distal area, and three with suggestive evidence of linkage (LOD>2.93) to bone size in one skeletal site. Our results indicated that the low power of QTLs mapping for composite phenotypic measurements may result from genetic heterogeneity of complex traits.




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