rs2472297

rs2472297 is a common variant in the bidirectional promoter region shared by CYP1A1 and CYP1A2 on chromosome 15q24, close to the aryl-hydrocarbon-receptor response elements that control how strongly these genes are switched on. It is the lead genome-wide-significant signal at this locus for measured caffeine metabolism: in a GWAS of up to 9,876 European-ancestry adults with independent replication, the T allele was associated with lower plasma caffeine (P = 1 x 10^-20) and a higher paraxanthine-to-caffeine ratio (P = 9 x 10^-22), both indicating faster conversion of caffeine to its first metabolite. A later multi-ancestry whole-genome-sequencing study put the per-allele effect at 0.142 standard deviations lower plasma caffeine (95% CI 0.10-0.18, P = 8 x 10^-12), roughly 0.7% of the variation in plasma caffeine. The T allele is common in European populations (about 21-24%) and close to absent elsewhere (about 0.1% in East Asian, 1-4% in African and South Asian reference populations), so this marker carries information only for people of European ancestry. It describes a tendency in clearance rate, not a measurement of caffeine sensitivity, and no intervention study has shown that this genotype changes how a person should time or limit caffeine.