Intronic variant in the OCT1 organic cation transporter reducing hepatic metformin uptake and altering response to multiple cation-transported drugs

Rare pathogenic PSEN1 missense variant substituting leucine for phenylalanine at position 177 in the gamma-secretase catalytic subunit; elevates Aβ42/Aβ40 ratio with relatively preserved total cleavage activity, classified as pathogenic for early-onset familial Alzheimer's disease

Downstream regulatory variant 10 kb 3' of PTPN1 (PTP1B) associated with type 2 diabetes risk (OR 1.43) and moderate obesity in a French population study; tags the regulatory region flanking the PTP1B negative-regulator locus

Intronic FLG-locus variant strongly associated with atopic dermatitis — the C allele marks filaggrin deficiency through a skin-specific mechanism with a larger effect size (OR 1.66) than the classical R501X null allele

Rare pathogenic missense variant in APP at the gamma-secretase cleavage site causing familial early-onset Alzheimer's disease with cerebral amyloid angiopathy; the "Calabrian" founder mutation originating in southern Italy over 1,000 years ago

Intergenic variant near LRRIQ3 associated with problematic opioid prescription use in a large GWAS; the T allele tags elevated risk of using opioids not as prescribed

Regulatory variant in SGK1 (serum/glucocorticoid regulated kinase 1) — the minor G allele is associated with improved insulin secretion in lean individuals and a modest reduction in type 2 diabetes prevalence, while also modifying blood pressure response to high dietary salt intake.

Rare pathogenic missense variant in APP near the gamma-secretase cleavage site causing autosomal dominant early-onset familial Alzheimer's disease; the "Australian" mutation first identified in an early-onset kindred, increasing amyloid-beta42/43 production 1.4- to 1.9-fold

Missense variant (Val179Ile) defining the CYP2E1*4 allele; associated with altered CYP2E1 enzyme activity affecting metabolism of acetaminophen, ethanol, isoniazid, halogenated anesthetics, benzene, and tobacco nitrosamines

Intergenic regulatory variant near the PRG2/PRG3 eosinophil granule protein cluster at chromosome 11; A allele may influence PRG2 expression and eosinophil major basic protein levels, implicated in eosinophil-mediated allergic inflammation and atopic disease susceptibility