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Title: A search for loci contributing to acquisition of peak bone mass
Author: Riddell, Claire Martha Majella
ISNI:       0000 0004 2725 1264
Awarding Body: Queen's University Belfast
Current Institution: Queen's University Belfast
Date of Award: 2011
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Background: Low peak bone mass is an important risk factor for osteoporotic fracture. Despite heritability of 50-85%, genetic studies have failed to identify a significant susceptibility locus. With advances in genotyping technologies, a genome-wide association (GWA) approach now allows an unbiased search for genetic determinants. Aim: To perform a GWA study using pooled DNA samples (as the cost of individual genotyping is prohibitive) to identify genetic loci associated with bone accrual in a cohort where all known confounding factors could be accounted for Methods: The Young Hearts 2000 Project carried out an in-depth survey of 1700 Northern Irish secondary school children. PIXI DXA scans of wrist and heel were performed and blood was collected. 1318 subjects had complete data available within separate age/sex groups: 12yr boys and girls, 15yr old boys and girls. BMD measurements were ranked after adjustments for age, BMI and pubertal status. Within each group, 50 subjects with the highest (controls) and 50 subjects with the lowest (cases) corrected BMD scores were selected giving a total of 400. DNA was extracted manually from stored buffy coat and pooled DNA was analysed using Illumina's HumanHap550 Genotyping BeadChip. The raw data for each SNP was compared between high and low BMD pools. Results: Clusters of SNPs that showed the greatest differences between high and low BMD pools were at Chr7 - GRM8, Chr8 - SGCZ, Chr15 - TRPM7 and Chr16 - TRAP1. These differences were confirmed on individual genotyping with p-values<0.05 for the SNPs within GRM8, SGCZ and TRAP 1. The SGCZ region showed the strongest association with BMD across the age groups. The TRAP 1 region was confirmed in replication pools. These genes each have described activity in bone and therefore are reasonable candidates for association with bone accrual and warrant further replication studies.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available