Abstract 791: Examining the roles of deleterious and potentially damaging variant alleles in African and Caucasian ancestral populations

Abstract

Abstract The purpose of this study was to analyze the overlap between potentially damaging Single Nucleotide Polymorphisms (SNPs) for coding gene regions across African American and Caucasian populations. Allele frequency and genotype data from the International HapMap Project was acquired for ancestral groups from Utah Residents with Northern and Western European Ancestry (CEU), Yoruba in Ibadan, Nigeria (YRI) and African Americans from the Southwest (ASW) resulting in 34,844 unique variants. Using the Variant Effect Predictor, non-synonymous SNPs in overlapping transcripts were filtered and found in 12,367 unique genes. SIFT or Polyphen-2 scores were used to determine which variants were likely to prove damaging to protein function, resulting in 10,917 variants. Functional annotation of biological pathways in genes affected by these variants was analyzed using DAVID. There was enrichment in olfactory pathways/g-protein coupled receptor function, cell membrane function and epidermal growth factor activity. Comparisons of genes affected by these deleterious variants were overlapped with the catalog of published genome-wide association studies (GWAS) with SNP-traits associated with cancer. There were 90 of 463 genes in common with this data that were examined for linkage disequilibrium with the damaging variants. Finally, SNPs with a variant allele frequency differences >±5% between CEU versus YRI or ASW resulted in with 2,381 SNPs with 55.7% overlap between groups. Analysis of patient genotypes found those in the CEU population were more likely to possess a homozygous allele. Using Chi-Squared tests, populations were examined for risk allele frequencies by genotype. This study demonstrated variants with potentially damaging consequences in cancer pathways are disproportionally represented in different ancestral populations. Citation Format: Myron K. Gibert, Luisel Ricks-Santi, John T. McDonald. Examining the roles of deleterious and potentially damaging variant alleles in African and Caucasian ancestral populations. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 791.