Missense variant in the IL-6 receptor that increases receptor shedding and enhances IL-6 trans-signaling; the C allele (358Ala) is paradoxically protective for coronary heart disease but increases risk for asthma and allergic disease, and predicts differential response to tocilizumab

Intronic variant in PTK2 (focal adhesion kinase) linked to restless legs syndrome through disrupted neuronal circuit development and sensory-motor signaling

Intronic MTRR variant associated with colorectal cancer survival in interaction with alcohol consumption

Causal frameshift polymorphism controlling IFNL4 protein production; the ΔG allele creates functional interferon lambda 4 which paradoxically impairs hepatitis C clearance

Pathogenic glucokinase missense variant causing maturity-onset diabetes of the young type 2 (MODY2) — lifelong mild fasting hyperglycemia that rarely requires treatment and is frequently misdiagnosed as type 1 or type 2 diabetes

Final enzyme in melatonin synthesis; promoter variant reduces ASMT expression and lowers melatonin production, affecting sleep onset and circadian rhythm

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

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

Intronic variant in SIRT1 affecting NAD-dependent deacetylase expression and oxidative stress protection

Intronic RAD50 variant in the Th2 locus control region (RHS7); T allele alters SMAD3 and SP1 transcription factor binding, shifts DNA methylation at the IL13 promoter in cord blood, and is associated with elevated total IgE levels and atopic disease risk.