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Background Gallstones are abnormal masses caused by impaired metabolism of cholesterol, bilirubin, or bile salts in the gallbladder or biliary tract. ATP-binding cassette subfamily G member 8 (ABCG8) is a protein that regulates cholesterol efflux from the liver. Genome-wide association studies (GWAS) and meta-analyses of GWAS revealed the ABCG8 rs11887534 variant as the most common genetic determinant of gallstones in humans. These findings have not been extensively replicated in Taiwanese. Therefore, we appraised the relationship between gallstones and rs11887534 in a relatively large Taiwanese sample. Methods We retrieved data collected through questionnaires, physical and biochemical tests from the Taiwan Biobank Bank (TWB). The study participants comprised 7388 men and 13,880 women who voluntarily enrolled in the Taiwan Biobank project between 2008 and 2019. Gallstones were self-reported. Results The overall sample size was 21,268 comprising 938 gallstone patients and 20,330 non-gallstone individuals. Among the participants, 20,640 had the GG and 628 had the GC + CC genotype. At  p -value &lt; 0.05, the baseline genotypes and gallstone status between men and women were not significantly different. The risk of gallstones was higher in participants having the GC + CC compared to the GG genotype: odds ratio (OR); 95% confidence interval (CI) = 1.698; 1.240–2.325), but was lower in men compared to women (OR = 0.763; 95% CI = 0.638–0.913). Compared to men with the rs11887534 GG genotype, women with the GG and GC + CC genotypes had a higher risk of gallstone (OR; 95% CI = 1.304; 1.087–1.565 for GG and 2.291; 1.514–3.467 for GC + CC). The positive association between GC + CC and gallstones was retained after we restricted the analysis to the female participants (OR; 95% CI = 1.789 = 1.208–2.648). Hormone use was associated with an elevated risk of gallstones (OR; 95% CI = 1.359; 1.107–1.668). Relative to GG and no hormone use, we found a significantly high risk among hormone users with the GC + CC genotype (OR; 95% CI = 3.596; 1.495–8.650). Conclusions The rs11887534 GC + CC genotype was independently associated with a higher risk of gallstones. This risk was much higher among women, especially those who used hormones for various gynecological purposes.

Risk of gallstones based on ABCG8 rs11887534 single nucleotide polymorphism among Taiwanese men and women