Leveraging Ethnic Group Incidence Variation to Investigate Genetic Susceptibility to High-Grade Glioma [electronic resource].

9781303525018

1 online resource (29 p.)

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BACKGROUND: The age-standardized incidence rates of malignant glioma are approximately 2.75 and 1.75 times higher among Whites than Asians and African-Americans, respectively, yet currently known environmental risk factors cannot explain this incidence difference. We hypothesize that genetic regions containing SNPs with extreme differences in allele frequencies across ethnicities harbor glioma-related variants which drive this ethnic-group incidence variation. METHODS: To test this hypothesis, we used International HapMap Project data to identify 3,961 candidate SNPs with the largest allele frequency differences in comparing Whites to Asians and African-Americans, respectively, and tested these SNPs for association with glioma risk in a set of White cases and controls. Top SNPs identified in this discovery set were subsequently tested for association with glioma in five independent replication case-control sets. RESULTS: While 8 SNPs selected from our discovery set (P < 0.01) also showed associations with glioma in one or more replication datasets (P < 0.05), no SNP achieved significance in both the discovery and replication datasets after accounting for multiple testing. However, the most strongly associated SNP, rs879471, was found to be in linkage disequilibrium with a previously identified risk SNP, rs6010620, in RTEL1. We estimate rs6010620 to account for a glioma incidence rate ratio of approximately 1.46 for White relative to Asian individuals. CONCLUSIONS: We have applied a novel genetic epidemiological method to explore disease etiology according to international patterns of disease incidence. The described method presents a viable alternative to admixture mapping when admixed samples are not available, and may have value in other diseases with applicable epidemiologic patterns.

Books / Online / Dissertations & Theses

English

July 25, 2014

Thesis (M.P.H.)--Yale University, 2012.