Genetics Analysis of Bone Size Variation of Hip, Spine and Wrist in Human Pedigrees
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Authors
Deng, Xu-Tao
Issue Date
2001-05
Volume
Issue
Type
Thesis
Language
en_US
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Alternative Title
Abstract
Bone size is an important determinant of osteoporotic fracture. However, the importance of genetic factors in determining bone size variation is unknown. My purposes here are three-folded. 1) Estimate the heritability (h2) of bone size by adjusting for several significant factors such as age, sex and height. 2) Evaluate the significance of other factors, such as sex, age, height and weight, and particularly, the life-style factors (exercise, smoking and alcohol consumption) on bone size variation. 3) Search for QTLs linked to bone size of the hip, spine and wrist, adjusting for age, sex and weight as covariates. Sizes of hip, spine and wrist bones were measured by dual-energy X-ray absorptiometry (DXA). For 635 individuals from 48 human pedigrees, 204 markers from chromosome 9 to chromosome X were genotyped that define a ~10 cM resolution human index map. Adjusting for age, sex and weight as covariates, I performed variance component analysis of bone sizes as quantitative traits with a polygenic component of variation. I also performed two-point and multi-point linkage analyses using the variance component linkage analysis method implemented in SOLAR. In my analysis, heritabilities (h2) (± SE) were, respectively, 0.48 (0.09), 0.64 (0.08), and 0.60 (0.09) for the sizes of the hip, spine and wrist bones. In the multipoint analysis, the highest multipoint LOD score in our sample was 3.00 near marker D17S787 at chromosome 17q21.31-q23.3 with wrist bone size. At chromosome 19pl3.3-ql2 near marker D19S226, our sample gave a LOD score of 2.82 with hip bone size. A LOD score of 2.2 was obtained near marker 2.21 near marker D9S175 at chromosome 9p21.3-q21.31. Possible candidate genes included Collal (Type I Collagen) at Chromosome 17q21.3-q22. Our study represents an important step toward identifying genes contributing to osteoporotic fractures.
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Publisher
Creighton University
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