Gallstones or cholelithiasis are hardened deposits of digestive fluid that form in the gallbladder. As a consequence, the bile duct is blocked and bile cannot be released into the intestine, causing the symptoms. They can vary in size from small, like a grain of sand, to large, like golf balls.

It is one of the most common diseases worldwide with a prevalence varying between 5% and 25% depending on geographical origin, sex and age.

The main cause of gallstone formation is not entirely clear, although it is known to be caused by excess cholesterol or bilirubin in the bile. Also if the bile is not emptied properly or frequently enough. Certain people are more prone to develop them due to risk factors that have an important influence.

  • Sex: they are more frequent in women.
  • Pregnancy.
  • Hormonal treatments with estrogens.
  • Age.
  • Ethnic origin: being more frequent in Native Americans and less frequent in people of African origin.
  • Obesity.
  • Elevated cholesterol and triglyceride levels.
  • Rapid weight loss.
  • Hypercaloric diet.
  • Lack of physical activity.
  • Hemolysis and chronic bacterial or parasitic infections.

Gallstones are responsible for one of the most common diseases in the western world and are usually treated with surgery. In a GWAS-type study carried out with almost 30,000 cases and more than 700,000 controls, 26 loci associated with the condition have been identified. Among them, variants in the ASTB gene, which hinder the correct transport of bile acids and others associated with cholesterol homeostasis, stand out. The authors conclude that the variants found affect the amount of cholesterol secreted or the cholesterol/bile acid ratio, a mechanism that probably causes stone formation.


Many people with gallstones have no symptoms.

Gallstones are often discovered as a chance finding when abdominal x-rays are taken.

However, if a large stone blocks a tube or duct that drains the gallbladder, a cramping pain may occur in the middle to upper right part of the abdomen. This is known as biliary colic. This is called biliary colic. The pain goes away if the stone passes into the first part of the small intestine.

Symptoms that may occur include

  • Pain in the upper right or middle part of the abdomen for at least 30 minutes. The pain may be constant or cramping. It may be sharp or dull.
  • Fever.
  • Yellowing of the skin and whites of the eyes (jaundice).

Other less frequent symptoms may include:

  • Clay-colored stools.
  • Nausea and vomiting.


Genetic factors seem to play an important role in cholelithiasis, which makes its prevention more difficult. However, there are some recommendations to help avoid gallstones:

  • Maintain a healthy weight and avoid rapid weight loss.
  • Eat a healthy, balanced diet.
  • Exercise regularly.
  • Avoid certain medications (those to lower cholesterol or hormone therapy).

Number of observed variants

13.5 million variants

Number of risk loci analyzed in the study

21 loci


Ferkingstad E, Oddsson A, Gretarsdottir S, et al. Genome-wide association meta-analysis yields 20 loci associated with gallstone disease. Nature Communications. 2018 Nov;9(1):5101.

Portincasa, P., Moschetta, A. & Palasciano, G. Cholesterol gallstone disease. Lancet 2006;368 (9531):230-239.

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