Liver Fat

Likely-pathogenic VLCAD missense variant abolishing enzyme activity — carrier status relevant for reproductive counseling and newborn screening awareness

ACADVL missense variant (p.Phe458Leu) classified likely pathogenic for VLCAD deficiency; heterozygous carriers are asymptomatic but important to identify for reproductive counseling

Coding GCKR variant (Pro446Leu) that directly reduces GCKRP sensitivity to fructose-6-phosphate, constitutively activating hepatic glucokinase and producing the characteristic trade-off of lower fasting glucose and insulin resistance against higher triglycerides, CRP, and NAFLD risk

Chromatin remodeling variant near HMGA1 associated with waist-to-hip ratio and height

Promoter-region variant in MTTP that reduces hepatic MTTP transcription; the G allele (common) is associated with lower MTTP expression, impaired VLDL secretion, and increased hepatic triglyceride accumulation

Protective missense variant that reduces MTARC1 protein stability, cutting hepatic fat accumulation and lowering risk of NAFLD, NASH, and liver-related death

Intronic PPARG variant associated with rate of change in insulin sensitivity over time, independent of adiposity

Intronic PPP1R3B variant that increases hepatic glycogen accumulation, elevating liver enzymes and raising the risk of gallstones

Near-gene PPP1R3B variant used as primary tagging SNP in the Stender 2018 study; minor A allele promotes hepatic glycogen accumulation, elevating liver enzymes and raising the risk of hepatic glycogenosis and gallstones

Intronic variant in ABCB11 in strong linkage disequilibrium with G6PC2 regulatory SNPs; the A allele tags higher G6PC2 expression in pancreatic beta cells, elevating the fasting blood glucose set-point by ~0.065 mmol/L per allele

Lipid transport variant that impairs VLDL secretion, creating a paradoxical trade-off between liver and heart health

Regulatory variant that reduces MBOAT7 expression in the liver, impairing phosphatidylinositol remodeling and increasing risk of NAFLD, liver fibrosis, and hepatocellular carcinoma

Intronic UCP1 variant — the C allele is associated with reduced overweight risk and lower BMI, likely by influencing UCP1 expression in brown adipose tissue

Intergenic tag SNP in near-perfect linkage disequilibrium with the HSD17B13 splice variant (rs72613567); the G allele tags HSD17B13 loss-of-function and is associated with reduced risk of NAFLD, NASH, cirrhosis, and lower liver enzymes — effects entirely attributable to LD rather than independent function

Intronic GCKR variant in strong LD with the coding P446L substitution (rs1260326); the T allele increases hepatic glucokinase activity, lowering fasting glucose and insulin while raising triglycerides, CRP, and NAFLD risk — a striking metabolic trade-off driven by excess hepatic de novo lipogenesis