Rare CYP2D6 stop-gain variant (Glu418Ter) that eliminates enzyme activity, causing poor metabolism of opioids, antidepressants, antipsychotics, and tamoxifen

Intronic TCF7L2 variant tagging a distinct haplotype with emerging evidence for effects on beta cell transcriptional regulation through the Wnt/beta-catenin axis

Missense variant in core circadian clock gene PER2 that lengthens intrinsic circadian period and shifts chronotype toward eveningness

Synonymous PPARG variant where the T allele reduces type 2 diabetes risk and improves LDL and HDL cholesterol despite no amino acid change

Missense variant that reduces CETP enzyme activity, raising HDL-C and enlarging lipoprotein particles; the Val/Val (GG) genotype is enriched in Ashkenazi Jewish centenarians and associated with slower cognitive decline

Intronic variant in the mitochondrial biogenesis regulator NRF2, associated with endurance athletic performance and intermittent exercise capacity

Intronic variant in the RAD50/TH2LCRR region at 5q31.1 that tags an enhancer hub coordinating IL-4, IL-5, and IL-13 expression; the G allele is associated with elevated serum IgE and increased susceptibility to the atopic march (eczema → food allergy → asthma → allergic rhinitis) through amplified Th2 cytokine output

Intronic MAPT variant tagging the H1c sub-haplotype within the H1 clade, independently elevating risk for progressive supranuclear palsy and corticobasal degeneration through increased 4-repeat tau expression

Rare missense variant causing a Leu293Arg substitution in CYP3A4, associated with reduced enzyme activity and altered metabolism of tacrolimus, warfarin, and other CYP3A4 substrates; most frequent in East Asian populations

Regulates insulin signaling efficiency and cellular glucose uptake