Missense variant in insulin receptor substrate 1 that impairs tyrosine phosphorylation and PI3-kinase recruitment, reducing insulin signaling and increasing type 2 diabetes risk and oral antidiabetes drug failure

Intronic CYP2E1 variant tagging the *1B haplotype; C allele marks reduced CYP2E1 expression and is associated with adverse drug reactions during tuberculosis treatment

5' UTR variant in the APH1A gamma-secretase subunit gene, located 21 bp upstream of the translation start codon; studied alongside the -980C/G risk variant in sporadic Alzheimer's disease but not independently associated with disease risk

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

Intronic regulatory variant in FADS2 that tags a 10-SNP haplotype reducing basal FADS1 and FADS2 expression, lowering long-chain PUFA synthesis capacity and arachidonic acid levels; T allele carriers have lower D5D and D6D activity and reduced fasting insulin.

Longevity-associated intronic enhancer variant with 1.9-fold increased probability of reaching age 95

Promoter polymorphism affecting MMP3 enzyme expression levels, influencing cartilage degradation and connective tissue remodeling

Rare truncating variant in desmoplakin that creates a premature stop codon at position 72, disrupting cardiac desmosomal integrity and predisposing carriers to arrhythmogenic cardiomyopathy with predominantly left ventricular involvement.

Intronic PON2 variant associated with variation in serum paraoxonase activity; the T allele tags a haplotype with reduced PON2-mediated antioxidant protection in vascular cells and macrophages, modestly increasing susceptibility to oxidative stress-driven atherosclerosis

CETP promoter variant that raises HDL cholesterol by reducing cholesteryl ester transfer protein activity; A allele carriers show higher HDL-C but mixed cardiovascular outcome evidence.