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

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 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.

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

Intronic PPARG variant that accounts for ~7% of individual variation in body weight reduction during calorie restriction

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 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 in people with impaired glucose tolerance

Promoter variant affecting adiponectin secretion and metabolic syndrome risk

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

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

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 master regulator of brown/beige fat differentiation, GWAS-validated for migraine 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 significantly associated with individual variation in body weight reduction during calorie restriction; G allele also linked to elevated plasma renin activity

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 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 ischemic stroke risk; the C allele — present in roughly 14% of people globally and 20% of Europeans — is linked to elevated cerebrovascular risk