Fat builds up in the liver without heavy alcohol use behind it. A Korean study deliberately excluded everyone with obesity, diabetes, high cholesterol or metabolic syndrome from its search — because those conditions are themselves heritable, and a normal study risks finding their genetics instead of the liver disease's own. One variant survived that stricter test.
Nonalcoholic fatty liver disease (NAFLD) is fat accumulating in the liver in someone who drinks little or no alcohol — the same pattern of liver injury seen in heavy drinkers, without the drinking. Its prevalence is rising worldwide, and it is closely tangled up with other common conditions: obesity, type 2 diabetes, high cholesterol and metabolic syndrome are all known to raise NAFLD risk.
Obesity, diabetes, high cholesterol and metabolic syndrome are all themselves substantially heritable. An ordinary NAFLD genetic study — comparing people with fatty liver to people without, regardless of whether they also have these other conditions — risks finding genetic signal for the comorbidities rather than for the liver disease itself. A locus that raises obesity risk will look like a NAFLD locus in that kind of study, whether or not it does anything to the liver directly.
This study, in the Korean Genome and Epidemiology Study (KoGES) cohort, took a different approach: it selected 424 people with nonalcoholic fatty liver and 5,402 controls specifically without obesity, type 2 diabetes, dyslipidemia or metabolic syndrome, and excluded meaningful alcohol use from both groups. After adjusting for sex, age, BMI and waist circumference, one variant reached genome-wide significance: rs7996045 (P=2.3×10⁻⁸), sitting in an intron of CLDN10. The authors note this locus had not turned up in earlier NAFLD studies that did not exclude comorbidities — a signal that may have been masked by the confounding effect this study was specifically designed to remove.
CLDN10 encodes claudin-10, a protein that helps form tight junctions — the seals between adjacent cells that control what can pass between them. In the liver, tight junctions between bile-duct and liver cells help regulate bile flow and barrier function. The study identifies the locus and its statistical association; it does not establish the specific mechanism by which this variant might affect fatty liver risk, and this page does not claim more than the study itself found.
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 4 more positions 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.
Du M et al. 2026, Science advances rs17496758 (SIK3), rs1124874 (LINC02702), rs12747620 (ZDHHC18) — PMID:41686896
Chen Y et al. 2023, Nature genetics rs7661964 (MTTP) — PMID:37709864
This is a single-locus finding from one study. One genome-wide significant variant, in a cohort of 424 cases, is real but preliminary — it has not yet been replicated in an independent cohort, and the study itself reports several other variants with only "suggestive" (not genome-wide significant) association that this page does not include.
NAFLD is diagnosed by imaging or biopsy showing fat in the liver, not by genotype. This variant does not predict who will develop fatty liver, and it explains only a small, unquantified part of the disease's known heritability. The study's real contribution is methodological — showing that excluding NAFLD's own comorbid risk factors from the study design surfaces genetic signal that a less careful design would miss or misattribute — more than it is a large step toward genetic prediction of the disease itself.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Nonalcoholic Fatty Liver Disease (NAFLD) comes down to these specific, well-studied positions — not a diagnosis.
CLDN10 · rs7996045
See detailed info →SIK3 · rs17496758
See detailed info →LINC02702 · rs1124874
See detailed info →ZDHHC18 · rs12747620
See detailed info →Databases, guidelines and references
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Nonalcoholic Fatty Liver Disease (NAFLD). MyGeneLog™. https://www.mygenelog.com/conditions/nonalcoholic-fatty-liver-disease
Fat building up in the liver in someone who drinks little or no alcohol — the same pattern of injury seen in heavy drinkers' livers, without the drinking behind it. It is closely linked to obesity, type 2 diabetes, high cholesterol and metabolic syndrome.
Because obesity, diabetes, high cholesterol and metabolic syndrome are themselves substantially heritable. A genetic study that includes people with those conditions risks finding their genetics instead of fatty liver disease's own — this study excluded them specifically to isolate NAFLD's own genetic signal.
One genome-wide significant variant, rs7996045, in an intron of CLDN10 (P=2.3×10⁻⁸), in 424 people with fatty liver compared with 5,402 controls, all drawn from a Korean cohort without major NAFLD comorbidities.
No. NAFLD is diagnosed by imaging or biopsy, not genotype. This is one variant from one study, not yet replicated elsewhere, and it explains only a small, unquantified part of the disease's overall heritability.
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