Intronic CYP2D6 variant tagging East Asian *10-lineage suballeles; the C allele co-segregates with reduced-function haplotypes affecting metabolism of ~25% of prescribed medications

Pathogenic PSEN1 missense mutation (His163Tyr) that impairs gamma-secretase processivity, elevating the Aβ42/Aβ40 ratio and causing autosomal dominant early-onset familial Alzheimer's disease with average onset around age 51.

Factor V Leiden - blood clotting disorder affecting thrombosis risk

Pathogenic PSEN1 missense variant at codon 278 that disrupts gamma-secretase substrate processing, shifts amyloid-beta production toward longer amyloidogenic species (Aβ42, Aβ43), and causes autosomal dominant early-onset familial Alzheimer's disease typically presenting between ages 40 and 55.

Main type 2 diabetes risk variant - strongly modulated by dietary fat

Intronic variant in RTEL1 (regulator of telomere elongation helicase 1) associated with atopic dermatitis risk; the A allele increases AD susceptibility through impaired telomere-dependent immune cell renewal

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

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