Genetically predicted associations with colonic polyps

Background The high incidence and multifactorial etiology of colonic polyps, involving genetic, environmental, lifestyle, and metabolic factors, warrant systematic investigation of genetically predicted associations. We employed Mendelian randomization (MR) to investigate genetically predicted associations of genetically proxied exposures with colonic polyps.Methods Following STROBE-MR guidelines, we performed a two-sample MR analysis using publicly available genome-wide association study (GWAS) summary data. Instrumental variables were selected based on single nucleotide polymorphism (SNP). Associations were assessed using inverse variance weighting, with sensitivity analyses including MR-Egger, weighted median, and MR Pleiotropy RESidual Sum and Outlier (MR-PRESSO) to evaluate heterogeneity and pleiotropy.Results MR analysis provided genetic evidence suggesting genetically predicted associations for 25 exposures across six domains. Positive genetically predicted associations were observed for factors including air pollution, socioeconomic deprivation, smoking, picky eating, use of specific medications (ezetimibe, atorvastatin, insulin), and various comorbidities (e.g. ulcerative colitis, type 1 diabetes). In contrast, longer education, positive family relationships, walking, and melanocytic naevi showed inverse genetically predicted associations with colonic polyps.Conclusions This MR study identifies genetic correlates and potential indicators for colonic polyps. While these findings contribute to etiological understanding, they should be considered exploratory and hypothesis-generating, warranting independent validation in diverse populations.

Etiology · Genetic association · Genetic heterogeneity · Genome-wide association study · Heritability · Imputation (statistics) · Mendelian randomization · Single-nucleotide polymorphism · Trait · Colorectal Cancer Screening and Detection · Genetic factors in colorectal cancer · Inflammatory Bowel Disease