Missense variant in betaine-homocysteine methyltransferase that reduces enzyme throughput and influences homocysteine, betaine, and choline metabolite levels

Intronic PTPRS variant that tags elevated type 2 diabetes risk in both sexes through increased receptor protein tyrosine phosphatase sigma activity, which dephosphorylates insulin-signalling substrates and attenuates both pancreatic insulin secretion and peripheral insulin sensitivity

Promoter variant that reduces APOA2 expression by 30%; GG homozygotes consuming more than 22g saturated fat daily have 84% higher obesity odds than AA/AG carriers

3'UTR variant that increases glucocorticoid-resistant GRβ isoform expression, blunting cortisol signaling and HPA axis negative feedback

Intronic TSH quantitative trait locus in phosphodiesterase 8B — the G allele raises the thyroid set-point, increasing hypothyroidism risk and potentially affecting levothyroxine dose requirements

Intronic RAD50 variant in the Th2 locus control region (RHS7); T allele alters SMAD3 and SP1 transcription factor binding, shifts DNA methylation at the IL13 promoter in cord blood, and is associated with elevated total IgE levels and atopic disease risk.

Intronic variant in CD58 (LFA-3) that modulates T-cell costimulation and Treg function; the protective G allele raises CD58 expression and reduces multiple sclerosis risk

Intronic splice variant causing ~50% reduced CYP3A4 mRNA expression, affecting metabolism of ~50% of all prescription drugs

Intronic MTRR variant with sex-specific association with DNA methylation patterning in one-carbon metabolism

Common intronic variant in HNF4A associated with modestly elevated type 2 diabetes risk via reduced pancreatic beta-cell function; identified through GWAS in South Asian and European populations