Energy & Weight

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

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

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

Regulates insulin signaling efficiency and cellular glucose uptake

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

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

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)

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

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

Promoter variant affecting adiponectin secretion and metabolic syndrome 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

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

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

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

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

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

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

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

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

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

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

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

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

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