Bridging the gap by discerning SNPs in linkage disequilibrium and their role in breast cancer

Abstract

Breast Cancer is the most common cancer among women with several genes involved in disease susceptibility. As majority of genome-wide significant variants fall outside the coding region, it is likely that some of them alter specific gene functions. GWAS database was used to interpret the regulatory functions of these genetic variants. A total of 320 SNPs for breast cancer were selected via GWAS, which were entered into the SNAP web portal tool, to determine the one's found to be in Linkage Disequilibrium (r² < 0.80). The resulting 2024 proxy SNP's were processed in RegulomeDB to predict their regulatory role. Of these, 1440 produced a score ranging from 1-6, whereas the remaining produced no data. Only the variants under score 4 (cut-off value) in RegulomeDB has been studied further. From these variants, 221 had scores of less than 4, indicating a high degree of potential regulatory role associated with them. Further study revealed that 61 of the 221 SNPs were reported to be genome-wide significant for breast cancer, 52 to be associated with other diseases, 99 as unconfirmed for association with breast cancer, leaving only 9 to be novel proxy SNPs linked to breast cancer. Therefore, the study further confirmed postulation of non-coding variants being linked to disease risk thereby, requiring additional validation through genome-wide association studies to substantiate their underlying mechanism.

Keywords: Breast Cancer; Ensembl; GWAS; RegulomeDB; Single Nucleotide Polymorphisms.