Nutrition & Metabolism

Main type 2 diabetes risk variant - strongly modulated by dietary fat

Second TCF7L2 diabetes variant - compounds risk with rs7903146

Insulin sensitivity - affects how well your cells respond to insulin

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

APOE E2 variant - generally protective for cardiovascular health

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

Triglyceride metabolism - affects fasting triglyceride levels and cardiovascular risk

Intestinal fat absorption - affects how efficiently you absorb dietary fat

Reduces beta-carotene conversion to vitamin A (retinol) by ~32% per T allele, contributing to "poor converter" status for plant-based vitamin A

Reduces beta-carotene to retinol (vitamin A) conversion efficiency, contributing to the "poor converter" phenotype

Alters vitamin D binding protein affinity, affecting total and bioavailable 25-hydroxyvitamin D levels

Vitamin D binding protein variant that determines VDBP isoform, affecting vitamin D transport, bioavailability, and supplementation response

Influences vitamin D synthesis by regulating how much 7-dehydrocholesterol is available for conversion to vitamin D3 in the skin

Vitamin D receptor start codon variant — determines receptor protein length and transcriptional activity

Determines secretor status — whether ABO blood group antigens are secreted into bodily fluids, affecting gut microbiome, vitamin B12 levels, and infection susceptibility

Transcobalamin II variant affecting cellular delivery of vitamin B12 via holotranscobalamin binding efficiency

Primary intestinal and renal vitamin C transporter — variant reduces ascorbate absorption and reabsorption efficiency

Regulates expression of the alpha-tocopherol transfer protein, the key determinant of circulating vitamin E levels

Master regulator of iron absorption via hepcidin control — the strongest common genetic determinant of iron status

Primary variant causing hereditary hemochromatosis type 1, disrupting iron regulation and hepcidin signaling

Second most common hereditary hemochromatosis variant, mildly increasing iron absorption and modestly raising iron stores

Zinc transporter 8 variant affecting zinc loading into insulin granules, influencing insulin crystallization, secretion, and type 2 diabetes risk

The most strongly replicated obesity-associated variant, affecting body weight through reduced adipocyte thermogenesis

Intergenic variant 188kb downstream of MC4R affecting appetite regulation, meal size, and obesity risk

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

Controls the pancreatic beta-cell potassium channel that regulates insulin secretion and determines sulfonylurea drug response

Regulates insulin signaling efficiency and cellular glucose uptake

Most common alpha-1 antitrypsin deficiency variant causing protein misfolding, lung disease, and liver disease

Promoter variant affecting adiponectin secretion and metabolic syndrome risk

Common leptin receptor variant affecting satiety signaling and metabolic health

Beta-3 adrenergic receptor variant that impairs catecholamine-stimulated lipolysis and thermogenesis in visceral adipose tissue, increasing susceptibility to abdominal obesity and metabolic dysfunction

Promoter variant reducing UCP1 expression in brown adipose tissue, impairing cold-induced and postprandial thermogenesis and increasing visceral fat accumulation with age

Missense variant reducing mitochondrial uncoupling efficiency in white adipose tissue, lowering 24-hour energy expenditure and increasing visceral fat accumulation in Val homozygotes

Promoter variant in skeletal muscle uncoupling protein 3 that increases UCP3 expression and fatty acid oxidation, with associations with BMI, insulin resistance, and type 2 diabetes risk

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

Promoter variant that increases leptin gene expression in adipose tissue, elevating circulating leptin and raising obesity, insulin resistance, and metabolic syndrome risk

3'UTR variant in the appetite-suppression gene POMC that disrupts miRNA binding sites, altering mRNA stability and melanocortin satiety signaling

Common MC3R missense variant that reduces receptor expression and shifts nutrient partitioning toward fat storage, particularly when co-inherited with the Thr6Lys variant (rs3746619)

Synonymous exon 8 variant in perilipin 1 that tags a haplotype associated with fat mobilization efficiency and sex-specific obesity risk

Upstream regulatory variant near INSIG2 that influences lipogenesis control and has been associated with BMI, subcutaneous fat accumulation, and obesity risk in multiple populations

Missense variant in the ghrelin prepropeptide that impairs postprandial ghrelin suppression, increasing appetite, sugar intake, and metabolic syndrome susceptibility

Intronic GIPR variant that reduces functional GIP receptor expression via altered splicing, impairing the incretin-mediated insulin response while paradoxically lowering BMI

Promoter variant that increases resistin expression via Sp1/Sp3 transcription factor binding, elevating circulating resistin and promoting insulin resistance and inflammation

Intergenic variant between GRB14 and COBLL1 that acts as an eQTL for GRB14 in adipose tissue, shifting body fat toward peripheral (hip and limb) versus central (visceral) deposition

Intronic enhancer variant in RSPO3 that increases gene expression in adipocytes, promoting android (abdominal) fat distribution over gynoid (lower-body) fat

Intronic variant in the LYPLAL1 locus associated with waist-hip ratio and fat distribution, with sex-dimorphic effects strongest in women

Intronic variant in the master regulator of brown/beige fat differentiation, GWAS-validated for migraine risk and linked to impaired thermogenesis and blood pressure regulation

Second strongest obesity GWAS locus after FTO - influences hypothalamic appetite regulation

Top obesity GWAS variant near NEGR1 — affects hypothalamic appetite regulation and neuronal growth

Intronic enhancer variant in LRP1 that regulates receptor expression in brain and vasculature, linking migraine susceptibility to central leptin signaling and metabolic regulation

Hypothalamic appetite regulator variant linking obesity susceptibility to migraine risk via shared neural pathways

Activin A signaling variant near INHBA linking adipocyte dysfunction to shared migraine and type 2 diabetes risk

Rare AMPK beta-1 subunit variant linking central energy sensing to shared migraine and type 2 diabetes susceptibility

GWAS obesity locus near KCTD15 — modulates adipogenesis through AP-2 transcription factor regulation

GWAS obesity locus near ETV5 — affects hypothalamic appetite regulation and food reward circuitry via glucocorticoid signaling

Intronic GWAS obesity variant in MTCH2 — affects mitochondrial energy balance, adipogenesis, and fatty acid oxidation through CPT1 regulation

Adipocyte transcription factor variant influencing central fat distribution and modifying weight-loss response to dietary fat

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

MAPK signaling variant in MAP2K5 associated with BMI through altered adipogenesis via the MEK5-ERK5 pathway

Missense variant in the FUT2 fucosyltransferase enzyme that alters haptocorrin glycosylation and is one of the strongest genetic determinants of circulating vitamin B12 levels

Tag SNP in the NBPF3/ALPL locus on chromosome 1 — the strongest common genetic determinant of circulating vitamin B6 (PLP) levels, acting through alkaline phosphatase-mediated catabolism

Intronic variant near ALPL associated with increased alkaline phosphatase activity, lowering circulating PLP (the active form of vitamin B6) — those with two G copies have higher ALPL activity and lower plasma B6 levels

Missense variant in the FTCD enzyme that impairs one-carbon unit transfer from histidine catabolism into the folate pool, reducing arsenic methylation efficiency and increasing toxicity risk

Intronic CBS variant that tags the CBS locus in GWAS studies; associated with altered homocysteine metabolism capacity and one-carbon methylation efficiency

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

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

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 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

GIANT consortium GWAS obesity locus near GNPDA2 — affects hexosamine-pathway-mediated glucose homeostasis and adipogenesis, increasing BMI risk

Obesity GWAS missense variant in SH2B1 that impairs leptin signaling and increases visceral fat and type 2 diabetes risk

Obesity GWAS locus in a conserved BDNF enhancer - reduces hypothalamic BDNF expression and satiety signaling, increasing caloric intake and BMI

Obesity and waist circumference GWAS hit in NRXN3 — links reward-circuit synaptic function to appetite dysregulation and addictive eating patterns

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

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

Intergenic GWAS tag SNP near the BCO1 pathway, associated with circulating beta-carotene and retinol levels independently of the functional BCO1 coding variants

Intronic NOS3 variant that alters splicing factor binding and is associated with blood pressure and cardiovascular risk, with effects that are amplified by physical activity

Missense variant in the major renal urate transporter; the Arg265 (C) allele is associated with less efficient urate excretion, elevating serum uric acid and gout risk, with the strongest effects in East Asian populations and in women

Intronic NADSYN1 variant in the DHCR7/NADSYN1 vitamin D locus; T allele tags the lower-vitamin-D haplotype, reducing 7-dehydrocholesterol availability for skin vitamin D3 synthesis

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

Uromodulin promoter variant — strongest GWAS signal for chronic kidney disease risk, affecting salt handling and blood pressure via NKCC2

UMOD promoter variant affecting uromodulin expression, linked to CKD, salt-sensitive hypertension, and gout risk with paradoxical kidney stone protection

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

Intronic GWAS tag variant in the vitamin D binding protein gene, the strongest common genetic determinant of circulating 25-hydroxyvitamin D levels

Upstream regulatory variant in the URAT1 urate reabsorption transporter gene; the C allele increases SLC22A12 expression and renal urate reabsorption, elevating serum uric acid and gout risk, with the strongest effects in East Asian and African populations where the C allele predominates

Intronic variant in the OAT4 renal urate transporter that modulates uric acid reabsorption in the proximal tubule, with the C allele raising serum urate and increasing gout risk especially in diuretic users

Near-gene regulatory variant affecting vitamin D 24-hydroxylase expression — modulates the rate at which active vitamin D is degraded

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

Upstream regulatory variant that reduces BCO1 (BCMO1) catalytic activity by ~48%, independently limiting beta-carotene to vitamin A conversion; the top GWAS hit for circulating beta-carotene levels

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

Near-gene regulatory variant near FUT6 that reduces fucosyltransferase expression and lowers circulating vitamin B12 — especially common in Indians

Intronic regulatory variant in FUT6 that alters HNF4α binding and fucosyltransferase expression, influencing intestinal fucosylation and circulating vitamin B12 levels — especially relevant in South Asian populations

Intronic variant in the SVCT2 tissue vitamin C transporter — associated with differences in plasma vitamin C levels in the EPIC cohort

Intronic variant in the tissue vitamin C transporter SVCT2 — GG homozygotes carry ~24% higher plasma vitamin C levels than AA homozygotes

Intergenic variant on chromosome 11q13.4 associated with circulating vitamin B12 levels in genome-wide association studies; the A allele is linked to higher serum B12 concentrations

Intronic NOS3 variant associated with ankle-brachial index and peripheral arterial disease risk in hypertensive adults; G allele linked to lower peripheral blood flow

Intronic SLC2A9 variant tagging an independent urate-transport signal; the protective C allele (~26% global frequency) reduces serum uric acid by 0.23–0.46 mg/dL per copy — with a substantially stronger effect in women — and attenuates the hyperuricemic response to fructose; the major T allele confers elevated uric acid and increased gout risk, particularly in Europeans

Intronic NADSYN1 variant at the DHCR7/NADSYN1 vitamin D locus; A allele was the top GWAS hit for lower circulating 25-hydroxyvitamin D in Ahn et al. 2010 (P = 3.4×10⁻⁹), reducing 7-dehydrocholesterol availability for skin vitamin D3 synthesis

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

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

Upstream regulatory variant near BCO1 that reduces beta-carotene to vitamin A conversion efficiency by approximately 59%

Missense variant in the GLUT9 renal urate transporter; the T allele (Val→Ile substitution) reduces urate reabsorption in the proximal tubule, lowering serum uric acid and conferring protection against hyperuricemia and gout

Near-gene intronic variant in the DHCR7/NADSYN1 locus on chromosome 11 that tags lower circulating vitamin D3 synthesis capacity; a near-perfect proxy for the canonical vitamin D synthesis SNP rs12785878