Near-gene variant tagging the TMPRSS3 hearing loss locus on chromosome 21, associated with susceptibility to sensorineural hearing loss and carrier status for DFNB8/10 deafness

No-function CYP2C19 stop-gain variant — second most common loss-of-function allele, highest in East Asian ancestry

Pathogenic missense variant in the cobalamin-processing enzyme; homozygosity causes cobalamin C (cblC) disease with severe methylation and detoxification failure

Intronic PTPN1 tag SNP within the 100-kb T2D-risk haplotype block — carriers of the G allele have modestly higher PTP1B activity, reducing insulin and leptin signal duration and raising LDL cholesterol risk in lean individuals

Intronic variant in the PTCSC2 lncRNA that alters a FOXE1 enhancer element, modulating thyroid gland development and hypothyroidism risk

Promoter variant in STAT6 that alters transcription factor binding; the T allele is associated with reduced IFN-γ production in response to herpes simplex virus, forming a 6.87-kb haplotype with rs167769 that confers a 3.3-fold increased risk of eczema herpeticum in atopic dermatitis patients through enhanced Th2 signaling

Intronic variant in the super elongation complex gene AFF3; the T allele increases AFF3 expression and was one of three original genome-wide significant hits for educational attainment (Rietveld 2013), with replication in all subsequent large GWAS

Rare CYP2A6 missense variant (p.Thr294Ile) that likely reduces nicotine-metabolising enzyme activity, affecting smoking behaviour, cessation pharmacotherapy response, and metabolism of letrozole and tegafur

Reduces intestinal GCPII enzyme activity by 53%, paradoxically raising circulating folate and lowering homocysteine by slowing folate catabolism in the gut

Pleiotropic 12q24 locus variant in SH2B3 (LNK) modulating JAK-STAT cytokine signaling, with associations spanning blood pressure, type 2 diabetes, celiac disease, and coronary artery disease