Master mitochondrial biogenesis regulator — Ser482 variant reduces PGC-1alpha transcriptional activity, impairing mitochondrial production, aerobic capacity, and metabolic adaptation

Missense variant in IL-13 that enhances Th2 cytokine signaling, elevating serum IgE and increasing risk for atopic dermatitis, allergic rhinitis, and eczema; the minor A allele (Q130) confers risk while the common G allele (R130) is protective for atopic disease

Intronic tag variant in MTHFD1 in strong LD with the R653Q missense variant, affecting folate-dependent purine synthesis and maternal neural tube defect risk

Intronic MAPT variant whose T allele co-defines the H1c sub-haplotype, independently conferring OR 1.85 for progressive supranuclear palsy and OR 2.07 for corticobasal degeneration in the same meta-analysis validating rs242557

Promoter variant that reduces CYP2A6 expression by ~50%, slowing nicotine metabolism and altering response to several cancer and antiretroviral drugs

Intronic PTPN1 variant in the 100-kb haplotype block; T allele associated with more favorable cholesterol profile (lower total and LDL cholesterol) in lean individuals

Regulatory variant 2 kb upstream of APH1A where the C allele (paper's G, coding strand) increases YY1 transcription factor binding and drives ~2.7-fold higher APH1A transcription, elevating gamma-secretase activity, increasing Aβ42 production, and raising Alzheimer's disease risk.

A 3-bp deletion in intron 3 of FADS2 that reduces delta-6 desaturase activity, impairing conversion of the omega-3 precursor ALA to EPA and GLA to arachidonic acid; deletion carriers accumulate ALA in blood while producing less EPA, DPA, and DHA, with effects confirmed in a meta-analysis of 7 trials.

Intergenic regulatory variant downstream of PPARG associated with central obesity and fat distribution in GWAS analyses; shows markedly different allele frequencies across ancestry groups

Promoter variant at position -866 of UCP2 that controls mitochondrial uncoupling protein expression; the T allele (A in coding-strand notation) increases UCP2 transcription, lowering ROS production and reducing insulin resistance, while C-allele homozygotes have lower UCP2 activity and carry higher oxidative-stress burden