Novel approach to functional SNPs discovery from genome-wide data reveals promising variants for colon cancer risk

Elena E. Korbolina, Ilja I. Brusentsov, Leonid O. Bryzgalov, Elena Yu Leberfarb, Arina O. Degtyareva, Tatyana I. Merkulova

Research output: Contribution to journalArticlepeer-review

8 Citations (Scopus)


In the majority of colorectal cancer (CRC) cases, the genetic basis of predisposition remains unexplained. The goal of the study was to assess the regulatory SNPs (rSNPs) in the human genome and to reveal SRC drivers based on the available chromatin immunoprecipitation sequencing (ChIP-Seq, ChIA-PET) and transcriptional profiling (RNA-Seq) data. We combined positional (locations within genome regulatory elements) and functional (associated with allele-specific binding and expression) criteria followed by an analysis using genome-wide association studies (GWAS) and minor allele frequency (MAF) datasets. DeSeq2 analysis through 70 CRC patients reinforced the regulatory potential. rSNPs (1,476) that were associated with significant (P < 0.01) allele-specific events resulting in thirty that exhibited a link with CRC according to the MAF and 27, with a risk of malignancy in general according to GWAS. Selected rSNPs may modify the expression of genes for tumor suppressors and the regulators of signaling pathways, including noncoding RNAs. However, the rSNPs from the most represented group affect the expression of genes related to splicing. Our findings strongly suggest that the identified variants might contribute to CRC susceptibility, which indicates that aberrant splicing is one of the key mechanisms for unraveling disease etiopathogenesis and provides useful inputs for interpreting how genotypic variation corresponds to phenotypic outcome.

Original languageEnglish
Pages (from-to)851-859
Number of pages9
JournalHuman Mutation
Issue number6
Publication statusPublished - 1 Jun 2018


  • Allele-specific events
  • Colorectal cancer
  • Functional variants
  • Gene regulation
  • SNPs
  • colorectal cancer
  • gene regulation
  • allele-specific events
  • functional variants
  • SART3
  • Humans
  • Male
  • Polymorphism, Single Nucleotide/genetics
  • Genome, Human/genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Colonic Neoplasms/genetics
  • Gene Frequency
  • HCT116 Cells
  • Risk Factors
  • Genotype
  • Alleles


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