Fat Storage & Energy

A common 3'UTR variant in the liver-expressed adiponectin receptor 2 gene; the T allele is associated with reduced waist circumference and lower colorectal and gastric cancer risk, while the reference C allele is linked to higher liver enzyme elevations in type 2 diabetic subjects.

Intronic ADIPOR2 variant whose T allele reduces receptor expression in immune cells and is associated with dose-dependent cardiovascular disease risk in people with impaired glucose tolerance

GDF15 signal-peptide missense variant that tags a haplotype influencing circulating GDF15 levels — a stress-responsive cytokine driving appetite suppression, nausea, and cardiometabolic stress signaling via the brainstem GFRAL receptor

3'UTR variant in ADIPOQ that modulates adiponectin mRNA stability; the common C allele is associated with lower circulating adiponectin and higher type 2 diabetes and cardiovascular risk, while the minor T allele is protective for metabolic outcomes

Intronic ADIPOR2 variant co-associated with cardiovascular disease risk in individuals with impaired glucose tolerance, tagging a haplotype of reduced hepatic adiponectin signaling through the ADIPOR2 locus

PPARG promoter-region enhancer variant that reduces PPARgamma expression, increasing risk for metabolic disease, coronary artery disease, and impaired insulin signalling

5' UTR variant in RBP4 that influences expression of retinol binding protein 4, an adipokine associated with insulin resistance and type 2 diabetes susceptibility when elevated

Intronic ADIPOR2 variant associated with cardiovascular disease risk in individuals with impaired glucose tolerance, influencing adiponectin receptor 2 signaling and hepatic lipid and glucose metabolism

Intronic variant in the adiponectin receptor 2 gene; rare homozygotes showed a markedly elevated risk of progression from impaired glucose tolerance to type 2 diabetes in a single Finnish cohort study, though evidence remains emerging and unreplicated.

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

Intronic PPARG variant significantly associated with circulating vitamin D levels and longitudinal change in insulin sensitivity

PPARG 3'-flanking region variant — the G allele independently tags a PPARG regulatory haplotype associated with altered TZD (thiazolidinedione) insulin-sensitizing drug response and modified type 2 diabetes risk in lifestyle intervention cohorts

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

Intronic PPARG variant associated with differential weight loss response to caloric restriction and circulating vitamin D levels

Intronic PPARG variant in strong linkage disequilibrium with rs709158; the G allele associates with a protective effect against metabolic syndrome and modestly lower total cholesterol in large prospective data.

Intronic PPARG variant that accounts for ~7% of individual variation in body weight reduction during calorie restriction; the T allele also appears in PPARG haplotypes associated with metabolic and glucose traits across several populations

SREBF1 intronic/3'UTR variant affecting SREBP-1c expression, associated with type 2 diabetes susceptibility, insulin resistance, triglyceride levels, and liver fibrosis risk.

Intronic variant in ZMYM4, a chromatin-remodeling transcription factor whose locus is associated with body fat distribution (waist-hip ratio, BMI-adjusted waist circumference) and immune regulation; rare deleterious ZMYM4 variants are enriched in severely obese children.

Intronic variant in SLC11A2 (DMT1), the primary intestinal iron transporter, associated with altered iron absorption regulation and T2DM susceptibility through the iron-beta-cell axis

Intronic PPARG variant in a metabolic syndrome–associated haplotype block; the A allele is enriched in people without metabolic syndrome and co-segregates with the protective AGCC haplotype across the PPARG locus

Intronic PPARG variant associated with modest reduction in type 2 diabetes risk — located in the master regulator of adipogenesis and the pharmacological target of insulin-sensitizing thiazolidinedione drugs

Intronic variant in LPIN1 (lipin-1) associated with liver fat accumulation and MASLD risk; the T allele interacts with sedentary behavior to substantially amplify adult fatty liver risk, while being protective against fibrosis in children

Upstream promoter variant that reduces ADIPOQ transcription, lowering circulating adiponectin and increasing risk of type 2 diabetes under additive and dominant models

Intronic ADIPOQ variant in LD with the promoter region; the minor A allele is associated with reduced circulating adiponectin in women and altered adiponectin dynamics during weight loss

Synonymous coding variant in ADIPOR2 (Q265Q) that was co-associated with cardiovascular disease risk in the Finnish Diabetes Prevention Study alongside three other ADIPOR2 intronic variants, suggesting it tags an extended risk haplotype affecting adiponectin receptor 2 expression or function in people with impaired glucose tolerance

Intronic PPARG variant — carriers of the C allele have elevated fasting glucose and higher risk of converting from impaired glucose tolerance to type 2 diabetes; the effect is substantially reduced by increased aerobic physical activity

Promoter variant affecting adiponectin secretion and metabolic syndrome risk

Intronic PPARG variant in the same haplotype block as rs1175543; the C allele is protective against metabolic syndrome (p=0.011) and was one of six PPARG SNPs significantly associated with body weight reduction during calorie restriction

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

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

Insulin sensitivity - affects how well your cells respond to insulin

Intronic/promoter-region ADIPOQ variant where the A allele reduces circulating adiponectin, blunting insulin sensitization and raising cardiovascular and metabolic risk

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

Intronic variant in the adiponectin gene associated with lower circulating adiponectin levels, increased type 2 diabetes susceptibility in overweight individuals, and elevated subclinical cardiovascular risk; the G allele confers reduced adiponectin secretion and higher metabolic syndrome risk

3' UTR variant in the PGC-1alpha gene that may alter PPARGC1A mRNA stability or miRNA regulation, with potential downstream effects on mitochondrial biogenesis and fat oxidation capacity

SREBF1 3' UTR variant that subtly impairs SREBP-1c function, increasing risk for type 2 diabetes through reduced adiponectin secretion and impaired insulin-mediated lipogenic signalling

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

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

Promoter variant reducing adiponectin transcription, increasing T2D, NAFLD, and cardiovascular disease risk

Intronic variant in IGFBP3 — the gene encoding the main carrier protein for IGF-1 in circulation — associated with lower circulating IGFBP-3 levels in carriers of the G allele

Intronic PPARG variant associated with body fat percentage, impaired glucose tolerance, and metabolic syndrome risk

Intronic PPARG variant significantly associated with individual variation in body weight reduction during calorie restriction; G allele also linked to elevated plasma renin activity, suggesting altered PPARγ-mediated adipose-renin axis signalling

Regulatory variant near WNT5A linked to type 2 diabetes risk via impaired Wnt5a-mediated insulin secretion and adipose inflammation

PPARD 3'UTR variant that reduces fatty acid oxidation capacity and blunts the metabolic response to lifestyle intervention

3' UTR regulatory variant in LPIN2 (lipin 2) that alters fat distribution and insulin sensitivity, with risk for type 2 diabetes that is amplified by obesity

Intronic ADIPOQ variant that reduces circulating adiponectin levels in G allele carriers, blunting insulin sensitization, fatty acid oxidation, and lipid-lowering response to caloric restriction

Missense variant in MTTP (microsomal triglyceride transfer protein) at residue 128; the C allele (Thr128) is associated with reduced hepatic steatosis and lower LDL-cholesterol through a complex, incompletely characterized effect on triglyceride transfer activity

Synonymous PPARG variant where the T allele reduces type 2 diabetes risk and improves LDL and HDL cholesterol despite no amino acid change

Intronic cis-regulatory PPARG variant where the C allele recruits PR domain repressor proteins, reducing PPARG transcription in adipose tissue and impairing adipocyte differentiation, fat distribution, and insulin sensitivity

Intergenic regulatory variant downstream of PPARG associated with central obesity and fat distribution in GWAS analyses; shows markedly different allele frequencies across ancestry groups

Intronic variant tagging the HNF4A P2 promoter risk haplotype; C allele carriers show reduced pancreatic beta-cell HNF4A expression and modestly elevated type 2 diabetes risk

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

Rare missense variant in the ApoE receptor 2 (LRP8) ligand-binding domain, disrupting a conserved tryptophan involved in apolipoprotein E-mediated lipid uptake and cholesterol homeostasis in adipocytes and macrophages

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

Intronic PPARG promoter tagSNP associated with modest reduction in type 2 diabetes risk — co-identified with rs9817428 in the WHI postmenopausal cohort and located within the master regulator of adipogenesis and insulin sensitivity

Intergenic variant near the SFRP5 adipokine locus; the A allele is strongly enriched in African ancestry (~19% MAF) and absent in East Asian populations, tagging a regulatory region that may influence SFRP5 expression — the anti-inflammatory adipokine that suppresses pro-inflammatory Wnt5a signaling in adipose tissue

Intronic ANK1 variant at the NKX6-3/ANK1 type 2 diabetes locus; the T allele alters ANK1 expression in adipose tissue and skeletal muscle, impairing insulin-stimulated glucose uptake and insulin processing through a non-islet mechanism

Intronic PPARG variant in strong linkage disequilibrium with rs1175543; the G allele is associated with higher LDL-cholesterol and participates in multi-locus interactions affecting abdominal obesity, CRP, and metabolic trait variation.

PPARG PPARγ2 P2 promoter variant that reduces basal promoter activity, elevating LDL-cholesterol and increasing coronary artery disease risk independently of traditional cardiovascular risk factors

Intronic variant in ADIPOR2 (adiponectin receptor 2) associated with reduced insulin sensitivity and increased type 2 diabetes risk; the G allele impairs adiponectin-driven PPARα and AMPK signaling that governs fatty acid oxidation and hepatic glucose metabolism

Intronic variant in the adiponectin gene associated with circulating adiponectin levels, ischemic stroke risk, and metabolic cardiovascular traits; the C allele — present in roughly 14% of people globally and 20% of Europeans — is linked to lower adiponectin output and elevated cerebrovascular risk

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

Intronic PPARG tagSNP with cross-ethnic replication for type 2 diabetes risk — located in the master regulator of adipogenesis and insulin sensitivity