How Likely Are You to Develop Gallstones Based on Your Genetics?

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How Likely Are You to Develop Gallstones Based on Your Genetics?

Date of Content: March 4, 2024
Written by: Jess Gayo
Reviewed by: Maarit Tiirikainen, PhD



What are Gallstones?

Gallstones, often lurking without symptoms, can unleash excruciating pain when they block bile ducts. But did you know that your genetic makeup might play a significant role in their development? 

Gallstones, crystalline deposits formed within the gallbladder or bile ducts, pose a prevalent yet often silent threat to millions worldwide. These tiny pebbles, ranging from as small as a grain of sand to as large as a golf ball, can trigger intense pain and complications when they obstruct the flow of bile. 

While lifestyle factors such as diet and obesity are commonly associated with gallstone formation, emerging research suggests a strong genetic component in predisposing individuals to this condition. Understanding the intricate interplay between genetics and gallstone formation holds pivotal importance in both preventive strategies and personalized medical interventions. 

By unraveling the genetic underpinnings of gallstones, scientists aim to uncover novel therapeutic targets and refine risk assessment models, ultimately paving the way for more effective management and prevention strategies.


How are Gallstones Formed?

Gallstones, small, solid particles formed in the gallbladder, originate from imbalances in the components of bile, a digestive fluid produced by the liver. Bile typically contains cholesterol, bile salts, and bilirubin, a waste product from the breakdown of red blood cells. When the balance of these components is disrupted, gallstones can develop.

The most common type of gallstone, cholesterol stones, forms when bile contains too much cholesterol and not enough bile salts or when the gallbladder fails to fully empty. Over time, excess cholesterol in the bile crystallizes, leading to the formation of stones. Pigment stones, on the other hand, result from an excess of bilirubin in the bile. These stones are often smaller and darker than cholesterol stones and are commonly associated with conditions such as cirrhosis or blood disorders.

The process of gallstone formation is multifactorial, involving a complex interplay of genetic, environmental, and lifestyle factors. While genetics can predispose individuals to gallstone formation, dietary choices, obesity, rapid weight loss, certain medications, and underlying medical conditions also contribute to their development. Understanding these factors is crucial for preventing gallstone formation and managing associated complications effectively.

What are the Contributing Factors to Developing Gallstones?

Genetic Factors

A 2016 large-scale study also delved into the genetic factors contributing to gallstone disease. Researchers conducted a meta-analysis of multiple genome-wide association studies (GWAS) involving individuals of European ancestry, aiming to identify genetic risk factors associated with gallstone disease.

The study identified several genetic variants linked to an increased risk of gallstone disease. Notably, two single-nucleotide polymorphisms (SNPs) located within the ABCG8 gene, namely rs11887534 and rs4245791, showed independent associations with gallstone disease risk. The ABCG8 gene encodes a cholesterol transporter, and variants in this gene were previously implicated in gallstone disease risk. The newly identified SNPs further support the role of ABCG8 in cholesterol metabolism and gallstone formation.

Additionally, associations were found for SNPs in other genes involved in cholesterol metabolism and bile acid regulation, including TM4SF4, SULT2A1, GCKR, and CYP7A1.

These other genes implicated in the study also play crucial roles in cholesterol metabolism, bile acid synthesis, and liver function. Variants in these genes may influence bile composition and cholesterol levels, contributing to gallstone formation.

Researchers have uncovered new insights into gallstone development through a more recent 2018 study involving over 27,000 cases and almost 737,000 controls. This study identified 21 novel genetic variants associated with gallstone disease, shedding light on the genetic factors contributing to this common condition.

Of particular significance are two low-frequency missense variants in the SLC10A2 gene, which encodes the apical sodium-dependent bile acid transporter (ASBT). These variants, Pro290Ser (SNP rs56398830) and Val98Ile (SNP rs55971546) were found to increase the risk of gallstone disease. ASBT protein plays a crucial role in reabsorbing bile salts from the intestines, and impairment of this function may disrupt the enterohepatic circulation of bile acids, leading to gallstone formation.

Other genes with genetic variants implicated in gallstone disease include SERPINA1 (rs28929474) and HNF4A (rs1800961), as well as several previously reported variants involved in cholesterol homeostasis, such as in ABCB4 (rs4148808) ABCG8 (rs11887534)  and CYP7A1(rs6471717).

The study also highlighted the complex interplay between genetic factors, bile acid transportation, and cholesterol metabolism in gallstone formation. While serum cholesterol levels do not directly correlate with gallstone risk, variants affecting cholesterol secretion into bile, or bile acid synthesis, may contribute to gallstone formation.

Environmental Factors

Environmental factors play a significant role in influencing an individual’s likelihood of developing gallstones. These factors encompass various aspects of lifestyle, diet, and other external influences that can contribute to the formation of gallstones. Here are several key environmental factors:

  1. Dietary Choices: High intake of certain foods, particularly those high in cholesterol and saturated fats, can increase the risk of gallstone formation. Diets rich in red meat, fried foods, and processed foods have been linked to a higher prevalence of gallstones. Conversely, diets high in fiber, fruits, and vegetables have been associated with a reduced risk.
  2. Obesity: Excess body weight is a well-established risk factor for gallstones. Obesity is thought to promote gallstone formation through various mechanisms, including increased cholesterol secretion into bile, reduced gallbladder motility, and alterations in bile composition. Individuals with a body mass index (BMI) above the normal range are more likely to develop gallstones.
  3. Rapid Weight Loss: Crash diets or rapid weight loss regimens can disrupt the balance of bile components, leading to the formation of gallstones. When the body sheds weight too quickly, the liver releases extra cholesterol into the bile, which may exceed the bile’s capacity to dissolve it. This excess cholesterol can then precipitate and form stones.
  4. Physical Inactivity: Sedentary lifestyle habits, characterized by lack of exercise and prolonged periods of sitting, have been associated with an increased risk of gallstones. Regular physical activity helps maintain healthy body weight and may reduce cholesterol levels, thereby lowering the risk of gallstone formation.
  5. Medications: Certain medications, such as hormone replacement therapy, cholesterol-lowering drugs, and drugs used to treat obesity, may alter bile composition or gallbladder function, increasing the likelihood of gallstone formation. It is essential to discuss the potential side effects of medications with a healthcare provider.
  6. Smoking: Smoking has been identified as a risk factor for gallstone formation. The exact mechanisms by which smoking influences gallstone development are not fully understood, but it may involve alterations in bile composition or gallbladder motility. Quitting smoking may help reduce the risk of gallstones and improve overall health.
  7. Alcohol Consumption: Excessive alcohol consumption has been linked to an increased risk of gallstones, particularly in men. Alcohol may affect bile composition and gallbladder function, contributing to stone formation. Moderation is key, and individuals should adhere to recommended alcohol intake guidelines.

Understanding the impact of these environmental factors on gallstone formation is essential for implementing preventive strategies and lifestyle modifications. Consulting with a healthcare professional for personalized guidance is advisable, especially for individuals with underlying medical conditions or genetic predispositions.

Are Gallstones Dangerous to Your Health?

Gallstones can indeed pose significant health risks, particularly when they cause symptoms or complications. While many people with gallstones remain asymptomatic, others may experience intense pain and complications that require medical intervention. 

When gallstones block the bile ducts, they can lead to acute inflammation of the gallbladder, known as acute cholecystitis. This condition typically manifests with severe abdominal pain, fever, nausea, and vomiting. If left untreated, acute cholecystitis can progress to serious complications such as gallbladder perforation or infection.

Moreover, gallstones can obstruct the common bile duct, preventing the flow of bile into the intestine. This obstruction can result in a buildup of bile in the liver, leading to jaundice, a yellowing of the skin and eyes, and potentially severe infections. In some cases, gallstones may also cause pancreatitis, inflammation of the pancreas, when they block the pancreatic duct.

Although not all gallstones cause immediate harm, the potential for complications underscores the importance of addressing them promptly. Timely diagnosis and appropriate management can help prevent serious complications and improve outcomes. 

Individuals experiencing symptoms such as abdominal pain, fever, jaundice, or persistent nausea should seek medical attention promptly to determine the underlying cause, including the possibility of gallstones, and receive appropriate treatment.

Should Gallstones be Removed Immediately?

The decision to remove gallstones depends on several factors, including the presence of symptoms, the type of gallstones, and the risk of complications. While not all gallstones require immediate removal, those causing symptoms or complications typically necessitate intervention.

For individuals experiencing severe abdominal pain, fever, jaundice, or other symptoms indicative of gallstone-related complications, prompt medical attention is crucial. In such cases, surgical removal of the gallbladder, known as cholecystectomy, is often recommended to prevent further complications and alleviate symptoms. 

Cholecystectomy is considered a safe and effective procedure, with minimally invasive techniques such as laparoscopic surgery offering shorter recovery times and reduced postoperative pain.

However, for asymptomatic individuals with incidental discovery of gallstones, the decision to remove the gallbladder may vary. In many cases, asymptomatic gallstones do not require immediate intervention. Instead, healthcare providers may opt for a watch-and-wait approach, monitoring the condition over time and recommending treatment only if symptoms develop or complications arise.

Ultimately, the decision to remove gallstones is individualized and should be based on a thorough assessment of the patient’s symptoms, medical history, and overall health. Consulting with a healthcare provider is essential for determining the most appropriate course of action and ensuring optimal outcomes.

What are the Symptoms of Gallstones?

Gallstones can manifest with a variety of symptoms, ranging from mild discomfort to severe complications. The most common symptoms include:

  • Abdominal Pain: The hallmark symptom of gallstones is sudden, intense pain in the upper right or center of the abdomen, often radiating to the back or right shoulder. This pain, known as biliary colic, typically occurs after meals, especially those high in fat, and can last for several hours.
  • Nausea and Vomiting: Gallstone-related abdominal pain may be accompanied by nausea and vomiting, particularly as the pain becomes more severe.
  • Jaundice: In cases where gallstones obstruct the bile ducts, bile may accumulate in the bloodstream, leading to jaundice. This condition is characterized by yellowing of the skin and whites of the eyes, dark urine, and pale-colored stools.
  • Fever and Chills: If gallstones cause inflammation of the gallbladder (acute cholecystitis) or infection, fever and chills may occur in addition to abdominal pain.
  • Indigestion: Some individuals with gallstones may experience symptoms of indigestion, such as bloating, gas, and discomfort in the abdomen, especially after consuming fatty or greasy foods.
  • Back Pain: Gallstone-related pain may radiate to the back or between the shoulder blades, mimicking symptoms of other conditions such as muscle strain or spinal issues.
  • Unexplained Weight Loss: In cases where gallstones lead to persistent symptoms or complications, unexplained weight loss may occur due to dietary restrictions or malabsorption of nutrients.

Recognizing these symptoms is crucial for prompt diagnosis and appropriate management of gallstones. Individuals experiencing persistent abdominal pain, jaundice, fever, or other concerning symptoms should seek medical evaluation to determine the underlying cause and receive appropriate treatment.

What are Treatments for Gallstones?

Treatment options for gallstones depend on various factors, including the presence of symptoms, the type of gallstones, and the individual’s overall health. Here are several common treatments for gallstones:

  • Observation: Asymptomatic gallstones that do not cause any symptoms may be monitored without intervention. Regular follow-up appointments with a healthcare provider are essential to monitor for any changes or development of symptoms.
  • Lifestyle Modifications: Adopting a healthy lifestyle, including maintaining a balanced diet low in fat and cholesterol, exercising regularly, and avoiding rapid weight loss, can help prevent the formation of new gallstones and reduce the risk of complications.
  • Medications: In some cases, medications such as bile acid medications (ursodeoxycholic acid) may be prescribed to dissolve cholesterol gallstones in individuals who are not suitable candidates for surgery or prefer nonsurgical options. However, this treatment is typically reserved for small gallstones and may take months or even years to be effective.
  • Extracorporeal Shock Wave Lithotripsy (ESWL): This noninvasive procedure uses shock waves to break up gallstones into smaller pieces, making them easier to pass through the bile ducts. ESWL is most effective for individuals with smaller gallstones and can be used as an alternative to surgery in certain cases.
  • Surgery: Surgical removal of the gallbladder, known as cholecystectomy, is the most common and definitive treatment for gallstones, particularly when they cause symptoms or complications. Cholecystectomy can be performed using minimally invasive techniques such as laparoscopic surgery, which typically results in shorter recovery times and less postoperative pain compared to traditional open surgery.

Individuals experiencing symptoms such as abdominal pain, nausea, vomiting, jaundice, or fever should seek medical evaluation promptly to determine the most appropriate treatment for their condition. Consulting with a healthcare provider is essential for personalized guidance and management of gallstone-related issues.

Ways to Lessen the Possibility of Developing Gallstones

Reducing the risk of developing gallstones involves adopting healthy lifestyle habits and making dietary choices that promote gallbladder health. Here are several evidence-based strategies to lessen the possibility of gallstone formation:

Maintain a Healthy Weight

Obesity is a significant risk factor for gallstones, as excess body weight can increase cholesterol levels in the bile and decrease gallbladder motility. Aim to achieve and maintain a healthy weight through a combination of balanced diet and regular physical activity. Gradual weight loss is preferable to rapid weight loss, which can increase the risk of gallstone formation.

Follow a Balanced Diet

Consume a diet rich in fruits, vegetables, whole grains, and lean proteins while limiting intake of high-fat and high-cholesterol foods. Foods high in saturated fats, such as red meat, fried foods, and full-fat dairy products, may contribute to gallstone formation. Instead, opt for healthier fats found in sources such as olive oil, avocados, and fatty fish.

Increase Fiber Intake

Dietary fiber, found in fruits, vegetables, legumes, and whole grains, may help prevent gallstones by reducing cholesterol absorption in the intestines and promoting regular bowel movements. Aim for at least 25-30 grams of fiber per day to support digestive health and reduce the risk of gallstone formation.

Stay Hydrated

Adequate hydration is essential for maintaining optimal bile flow and preventing gallstone formation. Aim to drink plenty of water throughout the day, as dehydration can lead to concentrated bile, increasing the risk of gallstones. Limit intake of sugary beverages and alcohol, which may contribute to dehydration and other health issues.

Moderate Alcohol Consumption

Excessive alcohol consumption has been linked to an increased risk of gallstones, particularly in men. Limit alcohol intake to moderate levels, defined as up to one drink per day for women and up to two drinks per day for men, to reduce the risk of gallstone formation and other health problems.

Be Cautious with Rapid Weight Loss

Avoid crash diets or rapid weight loss regimens, as they can disrupt the balance of bile components and increase the risk of gallstone formation. Instead, focus on gradual weight loss through a combination of healthy eating and regular exercise.

Consider Vitamin C Supplementation

Some studies suggest that vitamin C supplementation may help reduce the risk of gallstone formation by increasing bile acid secretion and decreasing cholesterol saturation in bile. However, more research is needed to confirm these findings and determine the optimal dosage for gallstone prevention.

Regular Physical Activity

Engage in regular physical activity, such as brisk walking, jogging, cycling, or swimming, to support overall health and reduce the risk of gallstones. Exercise helps maintain a healthy weight, improves bile flow, and promotes digestive regularity, all of which can contribute to gallbladder health.

By incorporating these lifestyle modifications into your daily routine, you can lessen the possibility of developing gallstones and promote overall digestive health. However, it’s essential to consult with a healthcare professional before making any significant changes to your diet or exercise regimen, especially if you have existing health conditions or concerns about gallstone risk.

LifeDNA’s Gallstones Trait Report

Unlock the secrets of your genetic blueprint with LifeDNA’s Gallstones Trait Report. Our scientifically-backed and comprehensive Wellness Report provides valuable insights into your unique genetic profile, empowering you to make informed decisions about your health and well-being.

Understanding your genetic predispositions to conditions like gallstones is essential for optimizing your wellness journey. With LifeDNA, you’ll gain access to personalized recommendations tailored to your genetic traits, helping you mitigate risk factors and prioritize preventive measures.

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Start your wellness journey today and take control of your health with LifeDNA. Avail of our plans to unlock access to our comprehensive Wellness Report and gain valuable insights into your genetic makeup. Don’t wait – seize the opportunity to optimize your health and well-being with LifeDNA’s scientifically-backed solutions.


  • Gallstones, crystalline deposits in the gallbladder or bile ducts, can cause severe pain when they obstruct bile flow.
  • Genetics plays a significant role in gallstone development alongside lifestyle factors like diet and obesity.
  • Imbalances in bile components, such as cholesterol and bile salts, lead to gallstone formation.
  • Various genetic variants, including those in SLC10A2, ABCG8, SULT2A1, and GCKR, are associated with gallstone risk.
  • Lifestyle factors like diet, obesity, rapid weight loss, and physical inactivity also contribute to gallstone formation.
  • Gallstones can cause acute cholecystitis, jaundice, pancreatitis, and other complications.
  • Treatment options include observation, lifestyle modifications, medications, lithotripsy, and surgery.
  • Lifestyle modifications to reduce gallstone risk include maintaining a healthy weight, following a balanced diet, increasing fiber intake, staying hydrated, moderating alcohol consumption, avoiding rapid weight loss, and considering vitamin C supplementation.



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*Understanding your genetics can offer valuable insights into your well-being, but it is not deterministic. Your traits can be influenced by the complex interplay involving nature, lifestyle, family history, and others.

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