Gallstones are hardened deposits that form in the gallbladder. A genome-wide meta-analysis of 43,639 cases and 506,798 controls found 75 risk loci and implicated genes that control how the gut and gallbladder move.
Gallstone disease is the formation of hardened deposits, usually from cholesterol or bile pigment, in the gallbladder. The study behind this page describes it as polygenic — many genetic positions, each contributing a little — and set out to find the determinants earlier studies had missed.
The study began with 28,627 cases and 348,373 controls in UK Biobank, replicated its findings in a Scottish cohort (1,089 cases, 5,228 controls), and then combined its data with FinnGen in a meta-analysis of 43,639 cases and 506,798 controls. It identified 75 risk loci, 46 of them new. The genes near them clustered in four pathways: lipid homeostasis, glucuronidation, phospholipid metabolism and gastrointestinal motility.
The finding the study puts first is about movement. Two genes in new, replicated loci — ANO1 and TMEM147 — are expressed in the gallbladder and the gastrointestinal tract and both regulate gastrointestinal motility. The gallstone risk allele rs7599-A suppresses TMEM147 in the liver, which suggests the protein protects against stone formation; that position is not in this catalogue. The study also built a polygenic risk score: people in its highest decile had 6-fold higher odds of gallstones than those in the lowest, and a higher score went with higher body mass index, liver enzymes and C-reactive protein and lower lipoprotein cholesterol.
The three positions here are further associations from the same meta-analysis rather than the genes it highlights: rs2228375 (NUP153, odds ratio 0.95), rs56339318 (LIN28B, odds ratio 0.92) and rs736730 (near ARPC2, odds ratio 1.05). An odds ratio below 1 means the allele reported is the less common one among cases. Gallstones that have inflamed the gallbladder have a page of their own: cholelithiasis with acute cholecystitis.
Gallstones are found by imaging, usually an ultrasound — not by a genotype. None of the three variants on this page is used by any guideline to predict, screen for or diagnose them.
Many gallstones cause no symptoms at all. Pain in the upper right abdomen after eating, fever or yellowing of the skin are reasons to see a clinician promptly, and decisions about treatment, including whether to remove the gallbladder, belong with them. The study's own score was linked to higher body mass index, and that is a factor a person can work on; the positions here are population-level findings of small effect.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Gallstone Disease comes down to these specific, well-studied positions — not a diagnosis.
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Gallstone Disease. MyGeneLog™. https://www.mygenelog.com/conditions/gallstone-disease
Gallstone disease is the formation of hardened deposits, usually of cholesterol or bile pigment, in the gallbladder. Many cause no symptoms; some cause pain or inflammation of the gallbladder.
Partly. A genome-wide meta-analysis of 43,639 cases found 75 risk loci, each of small effect, and a combined score separated people noticeably: the top decile had 6-fold the odds of the bottom one.
The three positions here are mapped to NUP153, LIN28B and ARPC2. The genes the source study highlights, ANO1 and TMEM147, regulate gastrointestinal motility and are not among them.
No. They are population-level findings of small effect and no guideline uses them. Gallstones are found by ultrasound, and symptoms belong with a clinician.
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