Intronic SCARB2 variant associated with REM sleep behavior disorder risk via the lysosomal GBA-trafficking pathway — the molecular bridge between glucocerebrosidase delivery and alpha-synuclein clearance

Intronic ABCA7 variant tagging an expanded VNTR that disrupts amyloid-beta clearance by microglia and impairs neuronal phosphatidylcholine metabolism, increasing Alzheimer's disease risk approximately twofold

P2RX7 variant with a unique dual mechanism — gain-of-function in channel opening and loss-of-function in pore formation — associated with chronic pain susceptibility, neuroinflammation, and modulation of microglial signaling

Promoter variant affecting GTP cyclohydrolase 1 expression and pain sensitivity, with opposite effects in European vs African populations

Capsaicin receptor variant affecting heat and pain sensitivity

Intergenic eQTL near HLA-DQA1 that tags the DR15 haplotype (DRB1*15:01/DQA1*01:02/DQB1*06:02), the strongest genetic risk factor for multiple sclerosis, and is also associated with SLE and ulcerative colitis

Intergenic SNP between HLA-DQB1 and HLA-DQA2 that tags the DQB1*06:02 allele, the third component of the DR15 haplotype (DRB1*15:01/DQA1*01:02/DQB1*06:02), conferring risk for multiple sclerosis, SLE, and narcolepsy; the T allele is protective

Intergenic regulatory variant upstream of POU3F2 (BRN-2), a transcription factor critical for cortical neuron differentiation; the A allele (risk) is the most-replicated genome-wide significant hit for educational attainment, associated with approximately 1 month less schooling per allele via altered POU3F2 expression in fetal and adult brain

Intronic regulatory variant in PHACTR1 that controls endothelin-1 and arterial compliance; the A allele is one of the strongest migraine GWAS hits (OR ~1.08, P=1×10⁻⁴⁷) while the G allele shows the opposite pattern — protective against migraine but a major coronary artery disease risk factor, demonstrating striking pleiotropy across five vascular diseases