Gallstones and Your Genes: What a 71,384-Case Study Says About “Increased Likelihood”

Gallstones and Your Genes: What a 71,384-Case Study Says About “Increased Likelihood”

This article is for educational purposes only. It is not a substitute for advice from a licensed physician, board-certified medical geneticist, or board-certified genetic counselor. For any decisions about testing, treatment, or care, consult a qualified clinician. In emergencies, call 911.

Bottom line: Gallstone risk is polygenic. That means it is spread thinly across thousands of common gene variants, not carried by one gene. The largest study yet pooled 71,384 cases and 779,234 controls. It found 28 risk regions in the genome. Yet genes explain only about a quarter of total gallstone risk. And most gallstones never hurt anyone. In pooled cohort data, about 10 out of 100 people with silent stones had symptoms by 5 years. An “increased likelihood” result is a position in a spread, not a date with a surgeon.

What you’ll learn

• Why gallstone genes are liver transport genes, not gallbladder genes.
• What the 2025 meta-analysis of 71,384 cases actually reported.
• Why an ultrasound, and not a DNA kit, tells you if stones are there.
• How rapid weight loss and GLP-1 drugs compare with your score right now.

1. Not one gene: how a cholesterol pump sets the stage

Start with the plumbing, because the mechanism is simple. The gallbladder is a small sac under the liver. It stores bile, the fluid that helps you digest fat. Bile can hold only so much cholesterol in solution. When it holds too much, tiny cholesterol crystals form. A sluggish gallbladder then lets those crystals sit and grow into stones.

Two genes sit at the control point. ABCG5 and ABCG8 build the two halves of one pump. That pump pushes cholesterol out of liver cells and into bile. A common change in ABCG8, called D19H, makes the pump work harder. More cholesterol lands in the bile. The bile then crystallizes more easily.

A 2007 genome-wide scan found D19H first. It is still the strongest common gallstone variant known. People who carried D19H had an odds ratio of 2.2 for gallstone disease. An odds ratio is simply the odds in one group divided by the odds in another. A value of 2.2 means the odds were roughly doubled. The link was stronger for cholesterol stones, at 3.3.

That sounds dramatic. It is not the whole story, and the next point matters more.

Susceptibility is not the same as a single-gene disease

Many readers arrive with a one-gene mental model. Gallstones do not fit it.

• In autosomal dominant inheritance, one copy of a faulty gene from either parent is enough to cause the condition. Gallstones do not work this way.
• There is no 50 percent coin flip for each child.
• There is no “carrier” status, meaning a healthy person who quietly passes on one faulty copy.
• Risk is polygenic. Polygenic means risk is spread across many common variants, each nudging the odds a little.
• The consumer gallstone report many readers hold is built from more than 6,900 variants. No single one is “the gallstone gene.”

The size of the genetic share is worth stating plainly. Common changes in the ABCG8 pump carry most of the genetic risk. That genetic risk accounts for about 25 percent of total risk. So roughly three quarters of the risk sits somewhere other than your genes.

The gene list also grew over time. A 2016 meta-analysis added four new loci. A locus is just a spot on a chromosome that tracks with a trait. A 2018 study from deCODE genetics raised the count to 20 loci. That work also found rare changes in SLC10A2, a gene for a bile acid transporter in the gut.

One quick contrast helps readers who browse this site. Familial hypercholesterolemia shares the word cholesterol. But it concerns LDL cholesterol in blood and heart disease risk. This article concerns cholesterol crystallizing inside bile. Liver conditions such as MASLD, hemochromatosis and Wilson disease involve material piling up inside liver cells. Gallstones instead form in a hollow organ. Different compartment, different problem.

If your family history looks like this article’s example, bring it to your primary care clinician. A written history is more useful to them than a percentile.

Section recap: Gallstones start when bile carries more cholesterol than it can hold. The ABCG5/ABCG8 pump is the main genetic lever, but risk is spread across thousands of variants. Genes explain about a quarter of the total.

2. What the largest gallstone study ever run actually found

The current reference point was published on 14 September 2025 in BMJ Open Gastroenterology. It is worth naming clearly, because most gallstone pages cite nothing at all.

The study pooled two large biobanks. UK Biobank contributed 26,802 cases and 381,651 controls. FinnGen R11 contributed 44,582 cases and 397,583 controls. Together that is 71,384 cases and 779,234 controls. This is the largest gallstone genome-wide association study run so far. A genome-wide association study, or GWAS, scans millions of common gene variants across many people. It then asks which variants appear more often in people with the condition.

Here is what it reported:

• 28 risk loci, meaning 28 regions of the genome linked to gallstone disease.
• 60 independent significant variants inside those regions.
• 184 lead variants. A lead variant is the single strongest signal at one spot.

The confirmed genes fit one pathway

The study confirmed a familiar set of genes. Read together, they describe one story about cholesterol and bile acids rather than a random list.

Gene	What it does in plain terms	Verified effect size
ABCG5 / ABCG8	Pumps cholesterol from liver cells into bile.	Odds ratio 1.69 for rs11887534.
GCKR	Helps regulate glucokinase and blood fat handling.	Odds ratio 1.12 for rs1260326.
CYP7A1	Runs the first, rate-limiting step of bile acid production.	Odds ratio 1.11 for rs6471717.
SULT2A1	Adds sulfate groups to steroids and bile-related sterols.	Odds ratio 1.17 for rs2547231.
TM4SF4	A gut and liver membrane protein linked to gallstones.	Odds ratio 1.12 for rs9843304.

Look at those numbers again. Outside ABCG8, each odds ratio sits near 1.1. That is a very small nudge. It is exactly why thousands of variants must be summed before a score means anything.

The 2025 study also added two new names to the list: UGT1A4 and FADS1/3. The FADS1/3 signal returns in section 6, and it comes with a large caveat.

The cross-ancestry result, told honestly

The discovery data came from people of European ancestry. The authors then looked up their 28 lead variants in Biobank Japan. After correction for multiple testing, 18 of the 28 still held. Nine of those reached genome-wide significance.

That is real support for partial generalizability. It also means 10 of the 28 did not replicate. Both halves belong in the same sentence, and section 5 explains why that matters to you.

None of this is a clinical test. If a report has you worried, a primary care visit or a genetic counselor is the right next step.

Section recap: The 2025 meta-analysis of 71,384 cases found 28 risk loci, and confirmed genes that all touch cholesterol or bile acids. Most single variants shift odds by only about 10 percent.

3. How much risk is “increased likelihood”? People out of 100

This is the section that should lower the temperature. Two sets of numbers do the work.

Number one: how common gallstones are

Published US prevalence figures look wildly different. They are not contradicting each other. They are counting different things.

• The NIH’s NIDDK says gallstones affect 10 to 15 percent of the US population, or almost 25 million people. In plain terms, that is about 10 to 15 people out of every 100 US adults.
• A national survey scanned more than 14,000 adults by ultrasound. Age-standardized prevalence in men was about 9 out of 100 white men, 9 out of 100 Mexican American men, and 5 out of 100 Black men.
• Figures in women ran far higher. About 27 out of 100 Mexican American women were affected, along with 17 out of 100 white women and 14 out of 100 Black women.
• Insurance claims tell a different story. Diagnosed and billed gallstone disease in 2019 ran at 0.70 percent for commercial plans, 1.03 percent for Medicaid and 2.09 percent for Medicare.
• An early genetics paper put prevalence in industrialized countries at 10 to 20 percent.

Why the huge spread, from under 1 in 100 to nearly 27 in 100? The case definition changes the answer. Ultrasound screening finds stones in everyone who has them, including people with no symptoms. Claims data only count people who sought care and got a code on a bill. The gap between those two is the silent-stone population.

Two things are solid across all of it. Gallstones are common. And women are affected far more than men. One survey estimated 6.3 million men and 14.2 million women aged 20 to 74 with gallbladder disease.

Number two: how often silent stones turn into trouble

This is the more useful number, and it is the one almost no page gives you.

The idea that silent stones usually stay silent dates back to a 1982 paper. Its title says it well: “The natural history of silent gallstones: the innocent gallstone is not a myth”. The modern figures come from a 2026 meta-analysis. It pooled eight cohort studies covering 25,924 people whose gallstones were found by chance.

Progression to symptoms looked like this:

• About 10 out of 100 at 5 years. This estimate is tight, with a confidence interval of 10 to 11.
• About 19 out of 100 at 10 years.
• About 26 out of 100 at 15 years. Treat this one loosely. Its confidence interval runs from 12 to 40 out of 100, so the true figure is quite uncertain.
• About 2 out of 100 per year overall.

Flip those around. At 5 years, roughly 90 out of 100 people with silent stones still had no symptoms. The authors also note the honest other half: risk does climb with longer follow-up. A separate expert review reports that up to 20 percent of adults develop stones, and more than 20 percent of those go on to symptoms. The timeframes differ, so the two sets of numbers do not have to match.

That natural history is exactly why the NIH states that gallstones without symptoms probably need no treatment.

Where a polygenic score fits

A polygenic score moves your position within that distribution. It does not tell you which side of it you land on. Most people with a high score will never have a gallbladder attack. A score is a percentile, not a verdict, and no guideline turns one into a care plan. Bring the report to your primary care clinician rather than to a search engine.

Section recap: About 10 to 15 out of 100 US adults have gallstones, and women far more than men. Among people with silent stones, roughly 90 out of 100 were still symptom-free at 5 years.

4. The test that diagnoses gallstones is an ultrasound, not a DNA kit

For most genetic conditions, the DNA test is the diagnostic test. Gallstones are the exception, and the difference is sharp.

The NIH is blunt about it: ultrasound is the best imaging test for finding gallstones. A transabdominal ultrasound is a painless scan through the skin of the belly, using sound waves. It answers in minutes a question no genotype can answer: are there stones in there right now? An expert review lists the same first step, alongside symptoms and liver blood tests.

Three very different things a reader may be holding

• A consumer polygenic report. The gallstone report sits under polygenic reports in the health predisposition catalog, not with the single-variant reports. It is a probability estimate relative to a population. It runs on a genotyping array. It is not a diagnostic device.
• Clinical imaging. Ultrasound comes first. The NIH also lists CT, which can miss some stones, MRI, which can show stones in the bile ducts, a HIDA scan, and ERCP. ERCP is more invasive and is used selectively, usually to remove a stone stuck in the main bile duct.
• Clinical genetic testing. For ordinary gallstone disease this is generally not indicated. It is reserved for rare single-gene bile disorders, which look clinically very different.

Two blunt statements follow from that list. An increased-likelihood result is not by itself a reason to ask for a scan. And a clean ultrasound today does not promise that stones will never form later.

So what is the right move? Take the report and your family history to primary care. If you want help reading any genetic result, you can find a board-certified genetic counselor through NSGC.org. That is the person trained for this conversation.

Section recap: Ultrasound, not genotyping, determines whether gallstones exist. A consumer polygenic report estimates probability and is not a diagnostic test or a referral slip.

5. Reading your report: risk estimate, ancestry limits, and why this is not a VUS

Most of the fear around genetic results comes from mixing up three different kinds of document. They are not interchangeable.

Type of result	What it tells you	What clinicians do with it
Polygenic risk estimate	Your position in a population spread, summed over thousands of variants.	Nothing standard yet. It is not a diagnosis.
Pathogenic single-gene result	One specific change, from a clinical lab, known to cause disease.	Triggers established management and family testing.
Variant of uncertain significance	A change whose meaning is unknown; a VUS may be reclassified later.	Care is not changed on the basis of a VUS.

One detail surprises people. A polygenic score does not produce a VUS at all. So a reader holding both a clinical panel result and a consumer report is reading two genuinely different documents. The professional body for medical genetics in the US, the ACMG, has published a points-to-consider statement on the clinical use of polygenic risk scores. Points to consider is not the same as an endorsement, and that distinction is the point.

The ancestry ceiling, with a concrete example

Vague warnings that scores “transfer imperfectly” are easy to ignore. Here is something sharper.

• The 2025 discovery cohorts were European-ancestry.
• In the Biobank Japan look-up, 18 of the 28 lead variants held after correction, and 9 reached genome-wide significance. The other 10 did not.
• In a large 2016 meta-analysis, the two ABCG8 variants were linked to higher risk in African American and Hispanic American participants. The GCKR variant rs1260326 showed the opposite direction in those groups.

Read that last bullet again. The same variant pointed the other way in a different population. That is not a rounding error. It is a reason to treat a percentile as softer than it looks.

The consumer report lists six ancestry groups it was evaluated in, including European, Hispanic/Latino, East/Southeast Asian, South Asian, Sub-Saharan African/African American, and Northern African/Central and Western Asian. Listing an ancestry is not the same as having equal evidence in it. That mismatch is worth knowing before you read your percentile as a hard number. A genetic counselor can walk through what your specific report does and does not support.

Section recap: A polygenic estimate, a pathogenic variant and a VUS are three different documents. Effect sizes built in European cohorts can shrink, or even reverse, in other populations.

6. What moves the needle more than your genes right now

Here is the honest hierarchy. Several everyday exposures shift gallstone risk faster and harder than a polygenic score does. Remember that genes carry only about a quarter of total risk.

The recognized precipitants

The NIH’s own risk list names the two that matter most to anyone losing weight:

• Obesity, and rapid weight loss.
• Very-low-calorie dieting and weight-loss surgery, which also drive fast fat loss.
• Female sex, older age, pregnancy, and hormone therapy or birth control pills.
• Physical inactivity and features of metabolic syndrome.
• A family history of gallstones.

The mechanism is easy to picture. Fast fat loss dumps extra cholesterol into bile. Eating less also means the gallbladder squeezes less often. More cholesterol, less flushing, more time to crystallize.

The GLP-1 question, with both numbers

GLP-1 receptor agonists are the medicines many readers are taking for weight or diabetes. A 2022 meta-analysis in JAMA Internal Medicine pooled 76 randomized trials with 103,371 patients. Because the inputs were randomized trials, this is strong evidence, not just observation.

What it found:

• Overall relative risk of gallbladder or bile duct disease: 1.37. Relative risk compares the rate in treated people with the rate in untreated people.
• Gallstones alone: relative risk 1.27. Gallbladder inflammation: 1.36.
• In weight-loss trials specifically: relative risk 2.29, against 1.27 for diabetes and other uses.
• Higher doses and longer use showed stronger signals.

A relative risk of 2.29 sounds alarming on its own. It must be read next to the absolute numbers. The FDA prescribing information for semaglutide (WEGOVY) reports gallstones in 1.6 percent of treated adults and 0.7 percent of placebo patients. In plain terms, that is about 2 out of 100 versus about 1 out of 100. The difference is roughly 1 extra case per 100 people treated.

The label adds a point no article should skip. It states that substantial or rapid weight loss can itself raise gallstone risk. It then reports that gallbladder disease was still more common on the drug than on placebo, even after accounting for how much weight people lost. The label also advises gallbladder studies and follow-up if stones are suspected. Semaglutide is approved by the FDA and is listed as approved by Health Canada.

One gap deserves a flag. No study has yet examined GLP-1 exposure together with gallstone polygenic risk. They are two separate inputs, and nobody has measured them as a pair.

This is a conversation for the prescribing clinician, not a reason to stop a prescribed medicine. Do not change a dose based on an article.

Ursodiol, and the fish-oil signal

Ursodeoxycholic acid, sold as ursodiol or Actigall, is a bile acid medicine. The FDA label carries two narrow indications. One covers dissolving certain small, non-calcified gallbladder stones in people who would otherwise have surgery but cannot or will not have it. The other covers preventing gallstone formation in people with obesity who are losing weight rapidly. This is a prescription decision, not a self-service option, and safety beyond 24 months is not established. The NIH notes these medicines work best on small cholesterol stones, are used only in special situations, and that stones can come back. Canadian approval status for the weight-loss prevention use was not confirmed for this article.

Finally, the fish-oil finding from the 2025 study. Among carriers of the FADS1/3 high-risk allele rs174564, more oily fish intake tracked with lower gallstone risk. The reported relative risk was 0.952, with a confidence interval of 0.915 to 0.991. Read that carefully. It is roughly a 5 percent relative reduction, and the interval almost touches 1.0. It is an observational finding inside an association study. There is no trial behind it, and no guideline recommends supplements for gallstone prevention. Treat it as an interesting hypothesis, nothing more.

Section recap: Rapid weight loss and obesity are named risk factors, and GLP-1 drugs add roughly 1 gallstone case per 100 people treated. The oily-fish signal is an unproven hypothesis, not advice.

7. If stones do cause trouble: surgery numbers and the cancer question

Some stones do cause pain or complications. Knowing the scale helps.

How common gallbladder surgery is in the US

A 2024 analysis of national survey and claims data put yearly US totals at roughly:

• 2.2 million ambulatory care visits.
• 1.2 million emergency department visits.
• 625,000 hospital discharges.
• 2,000 deaths.
• About 605,000 outpatient keyhole operations, 280,000 inpatient keyhole operations and 49,000 open operations.

That is roughly 930,000 cholecystectomies a year. A cholecystectomy is surgery to remove the gallbladder. It is one of the most common abdominal operations in the country. The NIH calls gallbladder removal the usual treatment for gallstones that cause symptoms. Women had higher care rates, while death rates were higher among men. Stones that migrate into the main bile duct are a separate problem, usually handled with a scope rather than an operation. The serious complications to know are gallbladder inflammation, bile duct infection and gallstone pancreatitis.

The cancer question, kept in proportion

A 2025 analysis in Translational Oncology used Mendelian randomization. That method uses inherited variants as natural experiments, which helps separate genuine links from confounding. It found a link between gallstone disease and biliary tract cancer, meaning cancer of the gallbladder and bile ducts. A companion analysis identified five new risk regions for that cancer. Colocalization with liver gene-expression data showed shared signals at LRPPRC and ABCG5, the same pump gene from section 1. In tumor tissue, LRPPRC was turned up and ABCG5 turned down, both at P below 0.001.

Now the absolute numbers, which change how that reads. The American Cancer Society estimates about 12,640 new US cases of gallbladder and nearby large bile duct cancer in 2026, and about 4,590 deaths. Roughly 4 in 10 of those are gallbladder cancers, so about 5,000 a year. Set that against the roughly 25 million Americans with gallstones. The overwhelming majority will never develop this cancer.

Three guardrails belong with that finding:

• A population-level genetic signal is not a personal forecast.
• Nothing in this evidence shows that removing a symptom-free gallbladder prevents cancer.
• There is no effective screening test, which is why only about 1 in 5 of these cancers is caught early.

Any new or persistent upper-abdominal pain, fever or yellowing of the skin belongs in front of a clinician promptly, not in a search box.

Section recap: Gallbladder removal is among the most common US operations, at roughly 930,000 a year. The gallstone-to-cancer genetic link is real at population level, but the cancer itself stays rare.

8. Your kids, your siblings, and the insurance paperwork

For a polygenic result, family questions and paperwork questions are really one conversation.

What travels to your children

Children inherit half of each parent’s variants, but they do not inherit the parent’s score. The reshuffling is real. A parent in a high percentile can easily have a child below average. That follows directly from a score built on thousands of variants.

Cascade testing does not apply here. Cascade testing means offering relatives a test for one specific disease-causing variant found in the family. A polygenic score has no such variant to track, so there is no relative to warn.

What does travel usefully is the family history itself:

• Write down who had gallbladder disease or surgery.
• Write down the age at which each of them had it.
• Bring that page to your primary care visit.

A mother and a sister who both had surgery in their late forties and early fifties is real clinical information. A percentile is not.

The legal picture, stated with its limits

In the US, the baseline is the Genetic Information Nondiscrimination Act of 2008, or GINA:

• Health insurers may not use genetic information for coverage, underwriting or premium decisions.
• Employers may not use it in hiring, firing, promotion, pay or job assignment.
• GINA’s health insurance protections do not cover life insurance, disability insurance or long-term care insurance.
• Some states add their own protections in those lines, so the answer depends on where you live. This article does not assess any single state’s law.

That third bullet is the one that matters mid-application. A life-insurance medical is exactly the setting GINA does not reach.

Canada took a different route. The Genetic Non-Discrimination Act was assented to on 4 May 2017. Section 3(1) bans requiring anyone to take a genetic test as a condition of goods, services or a contract. Section 4(1) extends that to requiring disclosure of results. Section 5 bars collecting or sharing results without written consent. The definition of genetic test is broad enough to include a consumer report. The Act also amended the Canada Labour Code and the Canadian Human Rights Act. The Supreme Court of Canada upheld the challenged provisions in 2020.

Do not read the two regimes as equivalent. Canada’s law is a general ban across goods, services and contracts, rather than a carve-out by insurance line. Provincial rules and individual insurer terms still vary, and those were not verified here.

Disclosure to relatives is a personal choice. A probabilistic result carries no clinical duty to tell anyone. If the decision feels heavy, a genetic counselor or your primary care clinician can help you think it through. And name the anxiety loop for what it is: a percentile is not a prognosis.

Section recap: Children inherit variants, not scores, and cascade testing does not apply to polygenic results. GINA covers health insurance and employment, but not life, disability or long-term care cover.

Frequently asked questions

Will you definitely get gallstones if your report says increased likelihood?

No. A polygenic score shifts your position in a spread; it does not predict one person’s outcome. Gallstones are common, at roughly 10 to 15 out of 100 US adults. Even among people who already have silent stones, about 90 out of 100 had no symptoms at 5 years. Nothing in a consumer report changes what a clinician would do today.

Will your children inherit this?

They inherit half of your variants, but not your score. With risk spread over more than 6,900 variants, a high-scoring parent can easily have a below-average child. There is no carrier status and no 50 percent rule here. Families also share diet, body weight and activity levels, which matter at least as much. What is worth passing on is a written family history with ages, shared with their clinician.

Will this affect your health or life insurance?

In the US, GINA blocks health insurers from using genetic information for coverage, underwriting or premiums. It does not cover life, disability or long-term care insurance, and some states add protections of their own. In Canada, the Genetic Non-Discrimination Act bans requiring a genetic test or its disclosure as a condition of a contract. Provincial and insurer terms still vary. For a live application, ask the insurer and, if needed, a lawyer.

Can your employer find out?

GINA prevents employers from using genetic information in hiring, firing, promotion, pay and job assignment. In Canada, the 2017 Act also amended the Canada Labour Code so federally regulated employees need not undergo or disclose a genetic test. Neither law makes a consumer result invisible. Both limit what may be done with it.

Should you get a second opinion?

For a polygenic gallstone score there is no clinical opinion to second, because no guideline body recommends acting on one. The ACMG has published points to consider on polygenic scores rather than an endorsement. A second opinion is genuinely useful for a different question: whether symptoms warrant imaging, or how to manage stones already found. A board-certified genetic counselor, found through NSGC.org, can explain any report you are holding.

Summary: what to bring to your next visit

Gallstone genetics is good science. It is not yet a clinical instrument. The 2025 meta-analysis of 71,384 cases mapped 28 risk loci and confirmed that the biology runs through cholesterol handling and bile acids. But genes account for only about a quarter of total risk. No guideline turns a score into a care plan. And ultrasound remains the only test that shows whether stones exist.

The useful output of reading a report is a better-prepared appointment. Bring three things:

• A written family history of gallbladder disease, with ages.
• A note of your current weight-loss rate and all medications, including any GLP-1 drug.
• The actual report, not a summary of it.

Then ask one question. Given this family history and these medications, does anything about these symptoms or exposures change what you would do? That is a far better question than asking whether a high score means surgery.

This article is for educational purposes only. It is not a substitute for advice from a licensed physician, board-certified medical geneticist, or board-certified genetic counselor. For any decisions about testing, treatment, or care, consult a qualified clinician. In emergencies, call 911.

References

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2. Jiang Y, Chen H, Tian Q, et al. Genetic associations of cholelithiasis and biliary tract cancer. Translational Oncology. 2025;62:102533. https://pubmed.ncbi.nlm.nih.gov/40974978/
3. Buch S, Schafmayer C, Völzke H, et al. A genome-wide association scan identifies the hepatic cholesterol transporter ABCG8 as a susceptibility factor for human gallstone disease. Nature Genetics. 2007;39(8):995-999. https://pubmed.ncbi.nlm.nih.gov/17632509/
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6. National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health. Gallstones: Definition & Facts, Symptoms & Causes, Diagnosis, Treatment. https://www.niddk.nih.gov/health-information/digestive-diseases/gallstones
7. Everhart JE, Khare M, Hill M, Maurer KR. Prevalence and ethnic differences in gallbladder disease in the United States. Gastroenterology. 1999;117(3):632-639. https://pubmed.ncbi.nlm.nih.gov/10464139/
8. Unalp-Arida A, Ruhl CE. Burden of gallstone disease in the United States population: Prepandemic rates and trends. World Journal of Gastrointestinal Surgery. 2024;16(4):1130-1148. https://pubmed.ncbi.nlm.nih.gov/38690054/
9. Alzoubi M, Omar Saleh A, Omari FA, et al. Asymptomatic gallstones: Cumulative incidence proportion, incidence rate, and risk factors for symptoms development: Systematic review and meta-analysis. PLOS One. 2026;21(3):e0345462. https://pubmed.ncbi.nlm.nih.gov/41886405/
10. Gracie WA, Ransohoff DF. The natural history of silent gallstones: the innocent gallstone is not a myth. New England Journal of Medicine. 1982;307(13):798-800. https://pubmed.ncbi.nlm.nih.gov/7110244/
11. He L, Wang J, Ping F, et al. Association of glucagon-like peptide-1 receptor agonist use with risk of gallbladder and biliary diseases: A systematic review and meta-analysis of randomized clinical trials. JAMA Internal Medicine. 2022;182(5):513-519. https://pubmed.ncbi.nlm.nih.gov/35344001/
12. US Food and Drug Administration. WEGOVY (semaglutide) injection, full prescribing information, Warnings and Precautions 5.3, Acute Gallbladder Disease. https://www.accessdata.fda.gov/drugsatfda_docs/label/2025/215256s026lbl.pdf
13. US Food and Drug Administration / DailyMed. URSODIOL (Actigall) capsules, Indications and Usage. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=a061bb07-a85d-4b08-877f-ce02156f0de7
14. Lammert F, Gurusamy K, Ko CW, et al. Gallstones. Nature Reviews Disease Primers. 2016;2:16024. https://pubmed.ncbi.nlm.nih.gov/27121416/
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16. American Cancer Society. Key Statistics for Gallbladder Cancer (2026 estimates), with National Cancer Institute SEER Cancer Stat Facts for liver and intrahepatic bile duct cancer. https://www.cancer.org/cancer/types/gallbladder-cancer/about/key-statistics.html
17. National Human Genome Research Institute (NHGRI), National Institutes of Health. Genetic Discrimination and the Genetic Information Nondiscrimination Act of 2008 (GINA). https://www.genome.gov/about-genomics/policy-issues/Genetic-Discrimination
18. Parliament of Canada. Genetic Non-Discrimination Act, S.C. 2017, c. 3. https://laws-lois.justice.gc.ca/eng/AnnualStatutes/2017_3/page-1.html
19. 23andMe. Gallstones (Polygenic Report), Health Predisposition reports catalog. https://www.23andme.org/clinicians/genetic-reports/health-predispositions/

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Last updated: 2026-09-25

Author: genelumen editorial team. This article aggregates 19 sources from peer-reviewed medical literature and public health agencies (tier 1=13 / tier 2=5). Named sources include the NIH (NIDDK and NHGRI), the FDA, Health Canada, the American Cancer Society, and the ACMG.

This article is for educational purposes only and is not a substitute for medical advice from a licensed physician, board-certified medical geneticist, or board-certified genetic counselor. In emergencies, call 911 (US/Canada) or 119 (Japan).

Related: Genetic Diseases category

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