Missense variant in the extracellular domain of the IL-4 receptor alpha chain that alters Th2 immune signaling, associated with atopic asthma, rhinitis, and altered IgE responsiveness

Methionine synthase — uses B12 to convert homocysteine to methionine

Regulatory variant in the TSPAN2/NGF locus on chromosome 1p13; the C allele is one of the largest-effect migraine risk variants identified in the genome, with particular elevation of risk for migraine without aura through a peripheral trigeminal sensitization mechanism driven by nerve growth factor signalling

Missense variant that impairs PAX4's ability to repress insulin and glucagon promoters, reducing beta-cell mass and insulin secretion capacity; strongly associated with type 2 diabetes and younger age of onset in East and Southeast Asian populations

Intronic variant in MATE1, the renal and hepatic metformin efflux transporter; the A allele reduces tubular secretion, prolongs metformin retention, and enhances glucose-lowering response in type 2 diabetes

Missense variant (Pro10Leu) in melanopsin, the photopigment driving circadian photoentrainment; TT carriers show altered light-signaling amplitude and elevated seasonal affective disorder 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

Promoter-region variant in SIRT1 affecting deacetylase expression; T allele elevates SIRT1 levels and is associated with better cognition but increased metabolic and cancer risk; C allele is the common protective form

Intronic variant in the myosin heavy chain 15 gene associated with impaired coronary microvascular function and abnormal coronary flow reserve in men (OR 2.27)

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