Missense/splicing variant in sepiapterin reductase that reduces BH4 biosynthesis to ~15% of normal, impairing dopamine and serotonin production; causes dopa-responsive dystonia in biallelic carriers

Most critical pharmacogenomic variant causing complete loss of DPD enzyme function; increases fatal 5-FU/capecitabine toxicity risk 25-fold without dose reduction

Controls the pancreatic beta-cell potassium channel that regulates insulin secretion and determines sulfonylurea drug response

Adenosine A2A receptor variant that determines individual sensitivity to caffeine's effects on anxiety and sleep

Common regulatory variant at the APOA5-ZNF259 locus; G allele reduces ApoAV protein levels, impairing triglyceride clearance and raising plasma TG by ~13% per allele — one of the strongest common GWAS signals for triglycerides

Intronic PPARG tagSNP with cross-ethnic replication for type 2 diabetes risk — located in the master regulator of adipogenesis and insulin sensitivity

Regulatory SNP in the ADH5 promoter at a potential NF-kB binding site; the protective T allele reduces GSNOR expression, preserving the bronchodilator S-nitrosoglutathione and lowering childhood asthma risk

Intronic SNCA variant at the 5′ locus associated with REM sleep behavior disorder risk — the strongest genetic prodromal marker for Lewy body neurodegeneration

Phase II glucuronidation enzyme that metabolizes bilirubin and many drugs including irinotecan; reduced activity causes Gilbert syndrome and severe chemotherapy toxicity

Intronic MTR variant that tags the folate/B12-dependent remethylation locus and associates with altered one-carbon metabolic balance