Most heavy drinkers never develop cirrhosis, which is what made this disease worth a genetic search. The paper behind this page confirmed the field's leading known gene and found two more — and all three turn out to be lipid genes, not alcohol-metabolism genes.
Alcohol misuse is the leading cause of cirrhosis — permanent, irreversible scarring of the liver — and the second most common reason for a liver transplant in the Western world. But most people who drink heavily do not develop it, and that gap between exposure and outcome is exactly what makes a genetic search for this disease worthwhile: if drinking alone determined who progresses to cirrhosis, there would be little for genetics to explain.
The paper behind this page is named for what it found. In 712 cases and 1,426 controls of European descent, with validation in a further 1,148 cases and 922 controls from two independent cohorts, it confirmed the field's leading known risk gene, PNPLA3, and identified two new ones: TM6SF2, and — held on this page — rs626283 in MBOAT7.
What connects all three is not alcohol metabolism. None of them processes ethanol or acetaldehyde, the toxic intermediate the flush-reaction and ALDH2 genetics on this site are built around. All three are involved in lipid processing — how the liver builds, stores and moves fat. The paper's own conclusion is that lipid turnover is important in the mechanism of alcohol-related cirrhosis: not how the liver breaks alcohol down, but how it handles fat once alcohol has done its damage.
MBOAT7 encodes an enzyme involved in remodelling membrane phospholipids, and separately from this paper it has since been linked to other forms of fatty liver disease as well — a second line of evidence for the same gene mattering in liver injury more broadly, not only in the alcohol-driven form studied here.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 1 more position to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Ghouse J et al. 2024, Nature genetics rs28636836 (HSD17B13) — PMID:38632349
Cirrhosis is diagnosed through a combination of blood tests, imaging (ultrasound or elastography, which measures liver stiffness), and sometimes biopsy. Staging and management depend on how advanced the scarring is and what complications have developed — nothing here depends on a genotype. The only intervention proven to slow or halt progression at any stage is stopping alcohol use.
What this page cannot do. This variant shifts risk by a fraction in people who drink heavily; it does not identify safe drinking levels, and it is not used to decide who can drink without harm. If alcohol use and liver health are a concern, that is a conversation for a doctor, not something read off a genotype.
This site's ALDH2 deficiency page covers a completely different kind of alcohol-related genetics — how efficiently the body clears the toxic intermediate acetaldehyde, which shows up as facial flushing. The genes on this page do not touch that pathway at all; they act on lipid handling in the liver, downstream of however much alcohol and its byproducts have already done. The two are not in tension and do not inform each other.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Alcohol-Related Cirrhosis comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 1 of 4 linked studies with a resolved discovery ancestry.
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Alcohol-Related Cirrhosis. MyGeneLog™. https://www.mygenelog.com/conditions/alcohol-related-cirrhosis
No. This variant shifts risk by a fraction among people who already drink heavily; it does not predict an individual outcome and is not used to decide safe drinking levels. Less alcohol is safer for the liver regardless of genotype.
No, and they are unrelated. The flush reaction is about how efficiently the body clears a toxic alcohol byproduct, acetaldehyde. This page is about lipid processing in the liver, a separate pathway entirely — this site's ALDH2 deficiency page covers the flush genetics.
That is the paper's central and somewhat unexpected finding. All three genes it confirmed or found — PNPLA3, TM6SF2 and MBOAT7 — are involved in how the liver handles lipids, not in metabolising ethanol itself, which reframes the mechanism as downstream fat handling rather than alcohol clearance.
No. Separately from this study, MBOAT7 has since been linked to other forms of fatty liver disease as well, which supports a broader role for the gene in liver injury beyond the specific alcohol-driven form studied here.
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