Limits...
Quantitative trait loci for bone lengths on chromosome 5 using dual energy X-Ray absorptiometry imaging in the Twins UK cohort.

Chinappen-Horsley U, Blake GM, Fogelman I, Kato B, Ahmadi KR, Spector TD - PLoS ONE (2008)

Bottom Line: Intraclass correlations showed results for MZ twins to be significantly higher than DZ twins for all traits.Heritability results were as follows: spine, 66%; femur, 73%; tibia, 65%; humerus, 57%; radius, 68%.We have shown strong heritability of all skeletal sizes measured in this study and provide preliminary evidence that spine length is linked to the chromosomal region 5q15-5q23.1.

View Article: PubMed Central - PubMed

Affiliation: Twin Research and Genetic Epidemiology Unit, King's College London School of Medicine, St Thomas' Hospital, London, United Kingdom. usha.chinappen@kcl.ac.uk

ABSTRACT
Human height is a highly heritable and complex trait but finding important genes has proven more difficult than expected. One reason might be the composite measure of height which may add heterogeneity and noise. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) for lengths of spine, femur, tibia, humerus and radius. These were investigated as alternative measures for height in a large, population-based twin sample with the potential to find genes underlying bone size and bone diseases. 3,782 normal Caucasian females, 18-80 years old, with whole body dual energy X-ray absorptiometry (DXA) images were used. A novel and reproducible method, linear pixel count (LPC) was used to measure skeletal sizes on DXA images. Intraclass correlations and heritability estimates were calculated for lengths of spine, femur, tibia, humerus and radius on monozygotic (MZ; n = 1,157) and dizygotic (DZ; n = 2,594) twins. A genome-wide linkage scan was performed on 2000 DZ twin subjects. All skeletal sites excluding spine were highly correlated. Intraclass correlations showed results for MZ twins to be significantly higher than DZ twins for all traits. Heritability results were as follows: spine, 66%; femur, 73%; tibia, 65%; humerus, 57%; radius, 68%. Results showed reliable evidence of highly suggestive linkage on chromosome 5 for spine (LOD score = 3.0) and suggestive linkage for femur (LOD score = 2.19) in the regions of 105cM and 155cM respectively. We have shown strong heritability of all skeletal sizes measured in this study and provide preliminary evidence that spine length is linked to the chromosomal region 5q15-5q23.1. Bone size phenotype appears to be more useful than traditional height measures to uncover novel genes. Replication and further fine mapping of this region is ongoing to determine potential genes influencing bone size and diseases affecting bone.

Show MeSH

Related in: MedlinePlus

Graph of Spine Length vs. Age (showing line of best fit).The relationship between spine length and age is shown. Age accounted for 11% of the variation in spine length affecting the distribution in our sample. This variation was reduced to 8% after subjects over 70 years of age were removed.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2262137&req=5

pone-0001752-g004: Graph of Spine Length vs. Age (showing line of best fit).The relationship between spine length and age is shown. Age accounted for 11% of the variation in spine length affecting the distribution in our sample. This variation was reduced to 8% after subjects over 70 years of age were removed.

Mentions: The study used 3,782 normal Caucasian females, 18–80 years old, with whole body dual energy x-ray absorptiometry (DXA) data although the age was restricted to 70 years of age to exclude degenerative changes in analysis of the spine length measurement. Spine was also age-adjusted and residuals were used since age accounted for 11% of the variation in spine length affecting the distribution in our sample. This variation was reduced to 8% after subjects over 70 years of age were removed. Figure 4 illustrates the relationship between age and spine length.


Quantitative trait loci for bone lengths on chromosome 5 using dual energy X-Ray absorptiometry imaging in the Twins UK cohort.

Chinappen-Horsley U, Blake GM, Fogelman I, Kato B, Ahmadi KR, Spector TD - PLoS ONE (2008)

Graph of Spine Length vs. Age (showing line of best fit).The relationship between spine length and age is shown. Age accounted for 11% of the variation in spine length affecting the distribution in our sample. This variation was reduced to 8% after subjects over 70 years of age were removed.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2262137&req=5

pone-0001752-g004: Graph of Spine Length vs. Age (showing line of best fit).The relationship between spine length and age is shown. Age accounted for 11% of the variation in spine length affecting the distribution in our sample. This variation was reduced to 8% after subjects over 70 years of age were removed.
Mentions: The study used 3,782 normal Caucasian females, 18–80 years old, with whole body dual energy x-ray absorptiometry (DXA) data although the age was restricted to 70 years of age to exclude degenerative changes in analysis of the spine length measurement. Spine was also age-adjusted and residuals were used since age accounted for 11% of the variation in spine length affecting the distribution in our sample. This variation was reduced to 8% after subjects over 70 years of age were removed. Figure 4 illustrates the relationship between age and spine length.

Bottom Line: Intraclass correlations showed results for MZ twins to be significantly higher than DZ twins for all traits.Heritability results were as follows: spine, 66%; femur, 73%; tibia, 65%; humerus, 57%; radius, 68%.We have shown strong heritability of all skeletal sizes measured in this study and provide preliminary evidence that spine length is linked to the chromosomal region 5q15-5q23.1.

View Article: PubMed Central - PubMed

Affiliation: Twin Research and Genetic Epidemiology Unit, King's College London School of Medicine, St Thomas' Hospital, London, United Kingdom. usha.chinappen@kcl.ac.uk

ABSTRACT
Human height is a highly heritable and complex trait but finding important genes has proven more difficult than expected. One reason might be the composite measure of height which may add heterogeneity and noise. The aim of this study was to conduct a genome-wide linkage scan to identify quantitative trait loci (QTL) for lengths of spine, femur, tibia, humerus and radius. These were investigated as alternative measures for height in a large, population-based twin sample with the potential to find genes underlying bone size and bone diseases. 3,782 normal Caucasian females, 18-80 years old, with whole body dual energy X-ray absorptiometry (DXA) images were used. A novel and reproducible method, linear pixel count (LPC) was used to measure skeletal sizes on DXA images. Intraclass correlations and heritability estimates were calculated for lengths of spine, femur, tibia, humerus and radius on monozygotic (MZ; n = 1,157) and dizygotic (DZ; n = 2,594) twins. A genome-wide linkage scan was performed on 2000 DZ twin subjects. All skeletal sites excluding spine were highly correlated. Intraclass correlations showed results for MZ twins to be significantly higher than DZ twins for all traits. Heritability results were as follows: spine, 66%; femur, 73%; tibia, 65%; humerus, 57%; radius, 68%. Results showed reliable evidence of highly suggestive linkage on chromosome 5 for spine (LOD score = 3.0) and suggestive linkage for femur (LOD score = 2.19) in the regions of 105cM and 155cM respectively. We have shown strong heritability of all skeletal sizes measured in this study and provide preliminary evidence that spine length is linked to the chromosomal region 5q15-5q23.1. Bone size phenotype appears to be more useful than traditional height measures to uncover novel genes. Replication and further fine mapping of this region is ongoing to determine potential genes influencing bone size and diseases affecting bone.

Show MeSH
Related in: MedlinePlus