Second independent FOXO3 longevity signal tagging a distinct intronic haplotype block with centenarian enrichment across Caucasian populations

Intronic variant near the CNR1 exon 3 alternative promoter that modulates CB1 receptor mRNA isoform balance; the C (risk) allele is associated with greater hippocampal volume loss in heavy cannabis users, heightened cannabis withdrawal and craving

Missense variant in kinesin family member 6; the Arg allele was associated with elevated coronary heart disease risk and with substantially greater benefit from statin therapy in the CARE, WOSCOPS, PROSPER, and PROVE IT-TIMI 22 trials, though a large meta-analysis of 19 case-control studies found no independent CAD risk association

Promoter variant in the NFAT binding site that increases IL-17A transcription, elevating Th17-driven inflammation and autoimmune disease risk

Deep-intronic variant in the CD226 (DNAM-1) co-stimulatory receptor gene associated with rheumatoid arthritis, multiple sclerosis, and altered neutrophil and white blood cell counts, likely acting as a regulatory variant that modulates CD226 expression in immune cells

Intronic variant in the androgen-regulating DENND1A gene associated with polycystic ovary syndrome (PCOS) risk; the G allele is linked to increased PCOS susceptibility and elevated post-load insulin levels, primarily in East Asian and Han Chinese populations

Intronic variant in the master regulator of brown/beige fat differentiation, GWAS-validated for migraine risk

Most common alpha-1 antitrypsin deficiency variant causing protein misfolding, lung disease, and liver disease

Pathogenic CYP1B1 missense variant (Arg469Trp) that severely reduces enzyme activity and is a leading genetic cause of primary congenital glaucoma, particularly in Middle Eastern, Iranian, and Pakistani populations

Intronic IL12B variant in linkage with the promoter-regulatory haplotype; T allele is protective against psoriasis and associated with better ustekinumab (anti-p40) response