Background: The genomic landscape of gallbladder disease remains poorly understood. We sought to examine the association between genetic variants and the development of cholecystitis.
Methods: The Biobank of a large multi-institutional health care system was used. All patients with cholecystitis were identified using International Statistical Classification of Diseases, 10th Revision, codes and genotyped across six batches. To control for population stratification, data were restricted to that from individuals of European genomic ancestry using a multidimensional scaling approach. The association between single nucleotide polymorphisms and cholecystitis was evaluated with a mixed linear model-based analysis, controlling for age, sex, and obesity. The threshold for significance was set at 5 × 10.
Results: Of 24,635 patients (mean ± SD age, 60.1 ± 16.7 years; 13,022 females [52.9%]), 900 had cholecystitis (mean ± SD age, 65.4 ± 14.3 years; 496 females [55.1%]). After meta-analysis, three single nucleotide polymorphisms on chromosome 5p15 exceeded the threshold for significance (p < 5 × 10). The phenotypic variance of cholecystitis explained by genetics and controlling for sex and obesity was estimated to be 17.9%.
Conclusion: Using a multi-institutional genomic Biobank, we report that a region on chromosome 5p15 is associated with the development of cholecystitis that can be used to identify patients at risk.
Level of evidence: Prognostic and epidemiological, Level III.