Epidemiology and Risk Factors of Gallstone Disease

Gallstone disease, or cholelithiasis, affects an estimated 10–20 per cent of adults in Western populations, with variations seen across age, sex and ethnic groups worldwide. Incidence rises with age and peaks between the fourth and sixth decades of life, with women exhibiting nearly twice the risk of men. Key drivers include obesity and metabolic syndrome, which promote hepatic cholesterol hypersecretion and bile supersaturation. Genetic susceptibility further modulates individual risk, with genome-wide studies identifying loci involved in lipid transport and bile acid metabolism. Hormonal factors—such as oestrogen exposure and parity—alter biliary lipid composition and gallbladder motility, while lifestyle influences including diet, sedentary behaviour and smoking also contribute. The balance of bile salts, phospholipids and cholesterol determines crystal nucleation and stone growth, with impaired gallbladder contractility exacerbating stasis. Globally, rising obesity and diabetes rates have driven an increasing burden of cholesterol gallstones, whereas pigment stones remain more common in regions with high rates of haemolytic disorders or biliary tract infection. Understanding the interplay of metabolic, genetic and environmental determinants is essential to inform targeted prevention strategies and to identify populations at greatest risk.

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Epidemiology and Risk Factors of Gallstone Disease publication trend

The graph below shows the total number of articles in epidemiology and risk factors of gallstone disease across all publications each year (not limited to Nature Index journals).

Technical terms

Gallstone disease (cholelithiasis): Formation of crystalline concretions in the gallbladder, predominantly from cholesterol supersaturation of bile.

Cholecystectomy: Surgical removal of the gallbladder, typically performed for symptomatic or complicated gallstones.

Mendelian randomization: A method using genetic variants as proxies for modifiable exposures to infer causal relationships with disease.

NPC1L1: Niemann-Pick C1-like 1 protein, a key mediator of intestinal cholesterol uptake.

STAT3: Signal transducer and activator of transcription 3, a transcription factor involved in inflammatory and metabolic signalling.

Cholesterol supersaturation: A biliary state in which cholesterol concentration exceeds solubilisation capacity, promoting crystal nucleation.

References

1. Gallstones, Cholecystectomy, and Kidney Cancer: Observational and Mendelian Randomization Results Based on Large Cohorts. Gastroenterology (2023).
2. Dietary diosgenin transcriptionally down-regulated intestinal NPC1L1 expression to prevent cholesterol gallstone formation in mice. Journal of Biomedical Science (2023).
3. Obesity, Type 2 Diabetes, Lifestyle Factors, and Risk of Gallstone Disease: A Mendelian Randomization Investigation. Clinical Gastroenterology and Hepatology (2021).
4. Factors Influencing Gallstone Formation: A Review of the Literature. Biomolecules (2022).
5. Sex and ethnic/racial-specific risk factors for gallbladder disease. BMC Gastroenterology (2017).
6. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease. Nature Communications (2018).
7. Biliary lipids and cholesterol gallstone disease. Journal of Lipid Research (2008).