Lipid & Fat Metabolism

Lipid metabolism and Alzheimer's risk - E4 carriers respond worse to high saturated fat

APOE E2 variant - generally protective for cardiovascular health

Promoter variant that reduces APOA2 expression by 30%; GG homozygotes consuming more than 22g saturated fat daily have 84% higher obesity odds than AA/AG carriers

Triglyceride metabolism - affects fasting triglyceride levels and cardiovascular risk

Intestinal fat absorption - affects how efficiently you absorb dietary fat

Omega-3 fatty acid conversion efficiency - affects ability to make EPA/DHA from plant sources

Regulatory variant in the FADS1 locus that controls delta-5 desaturase expression via promoter methylation, altering conversion of omega-6 and omega-3 precursors to long-chain PUFAs; the G allele drives higher arachidonic acid and cardiovascular risk while the T allele impairs EPA synthesis from plant-based omega-3

Intronic eQTL that reduces hepatic lipase expression, raising HDL-C levels while elevating triglycerides — with dietary fat type modifying the net cardiometabolic effect

Intronic variant in SCARB1 that affects SR-BI receptor function and the intestinal and hepatic uptake of fat-soluble vitamin E (alpha-tocopherol) and carotenoids from HDL particles

Near-gene variant influencing hepatic lipid metabolism; G allele raises triglycerides and LDL while A allele increases liver enzyme levels and fatty liver risk

Near-gene variant 30–44 kb downstream of TRIB1; A allele raises triglycerides, LDL, and total cholesterol, increases NAFLD risk, and is associated with longer sleep duration through a pleiotropic link between hepatic lipid metabolism and sleep regulation

Chromatin remodeling variant near HMGA1 associated with waist-to-hip ratio and height through transcriptional regulation in adipose tissue

Strongest genetic risk factor for non-alcoholic fatty liver disease, progression to cirrhosis, and hepatocellular carcinoma

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

Protective adenine insertion disrupting the HSD17B13 splice donor site, producing a truncated loss-of-function protein that reduces risk of NASH, alcoholic liver disease, cirrhosis, and hepatocellular carcinoma

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

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

Intronic PPP1R3B variant that increases hepatic glycogen accumulation, elevating liver enzymes and raising the risk of non-alcoholic fatty liver disease and 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, non-alcoholic fatty liver disease, and gallstones

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

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

APOL1 G1 kidney disease risk variant — missense change that evolved for trypanosome resistance but causes nephropathy in the recessive state

Second component of the APOL1 G1 kidney disease risk haplotype — a missense variant that, together with rs73885319 (S342G), confers 7- to 29-fold increased risk for non-diabetic CKD under a recessive inheritance model in African-ancestry populations

Six-base-pair in-frame deletion removing two amino acids from apolipoprotein L1, conferring trypanosome resistance but dramatically increasing chronic kidney disease risk in homozygous or compound heterozygous state with G1

Intronic regulatory variant that increases DAB2 expression in kidney tubules, amplifying TGF-β-driven fibrosis and raising chronic kidney disease risk