Allele frequencies of single-nucleotide polymorphisms associated with colorectal cancer in the kazakh population of Central Kazakhstan

Aim. To estimate the allele frequencies of single nucleotide polymorphisms (SNPs) associated with the risk of colorectal cancer (CRC) in the Kazakh population of Central Kazakhstan and compare the obtained results with international reference data.

Materials and methods. The study included 97 apparently healthy individuals with no diagnosed CRC or family history of malignant neoplasms, who self-identified themselves, their biological parents, and their maternal and paternal grandparents as Kazakh. Genotyping was performed using the TaqMan OpenArray platform. Following missingness control and assessment of genotype distributions for Hardy-Weinberg equilibrium, the data were harmonized with the 1000 Genomes Project Phase 3 reference dataset. The population position of the local group was assessed using principal component analysis and hierarchical clustering. For each SNP, absolute differences in allele frequencies between the local group and the Eurasian reference superpopulations were calculated, and the closest reference superpopulation was identified. Statistical outliers were excluded using Tukey’s fences. A total of 55 SNPs were included in the further analysis.

Results and discussion. Principal component analysis showed that the local group occupied an intermediate position within the Eurasian genetic space, predominantly between the European and East Asian superpopulations. In hierarchical clustering, the local group was represented in all four clusters, with most individuals distributed between two clusters of mixed population composition. The allele frequency profile of the analyzed SNPs showed pronounced locus-dependent variability. For 29 of the 55 SNPs (52,7%), the absolute allele frequency difference from the closest reference superpopulation did not exceed 0,025, whereas for 12 variants (21,8%) it was greater than 0,05. The closest reference superpopulation was EAS for 19 SNPs, EUR for 18 SNPs, and SAS for 18 SNPs.

Conclusions. The findings are consistent with the established understanding of the admixed genetic structure of the Kazakh population and demonstrate locus-dependent mosaicism in the allele frequency profile for the analyzed SNP panel. The nearly equal distribution of similarity across the Eurasian reference superpopulations indicates that no single reference superpopulation is the closest to the local group across the entire panel of variants. That should be taken into account while transferring findings from genome-wide association studies, applying polygenic risk scores, and planning medical genetic studies.

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