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Gallstone Genes

Gallstones are not something you usually think about — until something goes wrong. And then you think about them a lot! Ouch!


Your gallbladder is a small organ (~4 inches long) located on the upper right side of your abdomen, behind the liver. It stores bile, which your liver produces to break down fat in the foods you eat.

Gallstones (also called cholelithiasis) are hard ‘stones’ made of hardened bile. The composition of the stones can be either cholesterol or calcium bilirubinate. Cholesterol stones, the most common type, are thought to be formed if there is a lot of cholesterol in the bile. When the bile becomes supersaturated with cholesterol, the cholesterol can no longer be soluble in micelles (think oil droplets in water).[ref]

It is estimated that 10 – 40% of the population has gallstones, which are more common in women than in men. About 700,000 people each year in the US have their gallbladders removed.[ref]  That is a lot of people missing an organ…

Gallstones Genotype Report:

Unsurprisingly, the genetic link to gallstones centers around the genes that regulate cholesterol absorption from plants and cholesterol excretion from the body.

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Plant Sterols:
Conflicting information exists for plant sterols (from margarine or other foods labeled as “cholesterol-lowering plant sterols”) regarding gallstones and cardiovascular disease. The American Heart Association says plant sterols good for reducing cardiovascular disease. But the ABCG8 variants that increase the risk of gallstones due to increased absorption of sterols also increase the risk of cardiovascular disease.

Related article: Plant sterols and your genes.

Estrogens (natural or environmental):
Environmental factors that increase gallstones include estrogens (women have more gallstones), oral contraceptives, and hormone replacement therapy.[ref]

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Why join Genetic Lifehacks?

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Buch, Stephan, et al. “A Genome-Wide Association Scan Identifies the Hepatic Cholesterol Transporter ABCG8 as a Susceptibility Factor for Human Gallstone Disease.” Nature Genetics, vol. 39, no. 8, Aug. 2007, pp. 995–99. PubMed,

Di Ciaula, Agostino, et al. “The Role of Diet in the Pathogenesis of Cholesterol Gallstones.” Current Medicinal Chemistry, vol. 26, no. 19, 2019, pp. 3620–38. PubMed,

Di Ciaula, Agostino, and Piero Portincasa. “Recent Advances in Understanding and Managing Cholesterol Gallstones.” F1000Research, vol. 7, Sept. 2018, p. F1000 Faculty Rev-1529. PubMed Central,

Frank, Kurtis, et al. Tauroursodeoxycholic Acid Research Analysis. Jan. 2022.,

Goodloe, Robert, et al. “Lipid Trait-Associated Genetic Variation Is Associated with Gallstone Disease in the Diverse Third National Health and Nutrition Examination Survey (NHANES III).” BMC Medical Genetics, vol. 14, no. 1, Dec. 2013, p. 120. (Crossref),

Joshi, Amit D., et al. “Four Susceptibility Loci for Gallstone Disease Identified in a Meta-Analysis of Genome-Wide Association Studies.” Gastroenterology, vol. 151, no. 2, Aug. 2016, pp. 351-363.e28. PubMed,

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Paumgartner, G., et al. “Ursodeoxycholic Acid Treatment of Cholesterol Gallstone Disease.” Scandinavian Journal of Gastroenterology. Supplement, vol. 204, 1994, pp. 27–31. PubMed,

Rodriguez, Santiago, et al. “Lipids, Obesity and Gallbladder Disease in Women: Insights from Genetic Studies Using the Cardiovascular Gene-Centric 50K SNP Array.” European Journal of Human Genetics, vol. 24, no. 1, Jan. 2016, pp. 106–12. PubMed Central,

Tsai, Chung-Jyi, et al. “Weight Cycling and Risk of Gallstone Disease in Men.” Archives of Internal Medicine, vol. 166, no. 21, Nov. 2006, pp. 2369–74. Silverchair,

Wang, Siqi, et al. “Is the Oral Contraceptive or Hormone Replacement Therapy a Risk Factor for Cholelithiasis: A Systematic Review and Meta-Analysis.” Medicine, vol. 96, no. 14, Apr. 2017, p. e6556. PubMed,

Zhan, Lei, et al. “Prevalence of ABCB4 Polymorphisms in Gallstone Disease in Han-Chinese Population.” American Journal of Translational Research, vol. 8, no. 2, Feb. 2016, pp. 1218–27. PubMed Central,

About the Author:
Debbie Moon is the founder of Genetic Lifehacks. Fascinated by the connections between genes, diet, and health, her goal is to help you understand how to apply genetics to your diet and lifestyle decisions. Debbie has a BS in engineering from Colorado School of Mines and an MSc in biological sciences from Clemson University. Debbie combines an engineering mindset with a biological systems approach to help you understand how genetic differences impact your optimal health.