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

Intronic variant in serine racemase that alters D-serine production in pancreatic beta cells, modulating NMDA receptor signaling and glucose-stimulated insulin secretion; C allele associated with increased type 2 diabetes and gestational diabetes risk, particularly in East Asian populations

Regulatory variant 54 kb upstream of the aryl hydrocarbon receptor gene; the strongest GWAS signal for habitual caffeine intake, influencing AHR expression, CYP1A2 inducibility, and caffeine clearance capacity

Intronic variant near LIPG whose T allele increases circulating endothelial lipase levels and is associated with lower HDL cholesterol at genome-wide significance across multiple large cohorts

Missense variant reducing mitochondrial uncoupling efficiency in white adipose tissue, lowering 24-hour energy expenditure and increasing visceral fat accumulation in Val homozygotes

Regulatory variant near the NAF1 telomerase assembly gene associated with shorter telomeres, higher cardiovascular risk, and lower cancer risk

Missense variant in the IL-6 receptor that increases receptor shedding and enhances IL-6 trans-signaling; the C allele (358Ala) is paradoxically protective for coronary heart disease but increases risk for asthma and allergic disease, and predicts differential response to tocilizumab

Intronic variant in PTK2 (focal adhesion kinase) linked to restless legs syndrome through disrupted neuronal circuit development and sensory-motor signaling

Intronic MTRR variant associated with colorectal cancer survival in interaction with alcohol consumption

Pathogenic glucokinase missense variant causing maturity-onset diabetes of the young type 2 (MODY2) — lifelong mild fasting hyperglycemia that rarely requires treatment and is frequently misdiagnosed as type 1 or type 2 diabetes