Meta-analysis of genome-wide linkage studies for bone mineral density

Journal of Human Genetics
Young Ho LeeGwan Gyu Song

Abstract

Genome-wide linkage studies have shown several chromosome loci that may harbor genes that regulate bone mineral density (BMD), but results have been inconsistent. A meta-analysis was performed to assess evidence for linkage of BMD across whole genome scan studies. Eleven whole-genome scans of BMD or osteoporosis containing 3,097 families with 12,685 individuals were included in this genome scan meta-analysis (GSMA). For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted and summed across all studies. The summed rank for each bin was assessed empirically for significance using permutation methods. A total of seven bins lie above the 95% confidence level (P=0.05) and one bin was above the 99% confidence level (P=0.01) in the GSMA of eleven linkage studies: bins 16.1 (16pter-16p12.3, Psumrnk <0.01), 3.3 (3p22.2-3p14.1), 1.1 (1pter-1p36.22), 18.2 (18p11.23-18q12.2), 6.3 (6p21.1-6q15), 20.1 (20pter-20p12.3), and 18.1 (18pter-18p11.23). GSMA was performed with seven studies with linkage scores of LOD >1-1.85 for sensitivity test, confirming the linkage on chromosome 16p and 3p and revealing evidence of new linkage in bins 10.2 ...Continue Reading

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