Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) As Determinants of Habitual Caffeine Consumption

We report the first genome-wide association study of habitual caffeine intake. We included 47,341 individuals of European descent based on five population-based studies within the United States. In a meta-analysis adjusted for age, sex, smoking, and eigenvectors of population variation, two loci achieved genome-wide significance: 7p21 (P = 2.4×10−19), near AHR, and 15q24 (P = 5.2×10−14), between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2.本研究首次针对习惯性咖啡因摄入量开展全基因组关联研究（genome-wide association study）。本研究基于美国境内五项基于人群的研究，纳入了47341名欧洲血统个体。在针对年龄、性别、吸烟状况以及人群变异特征向量进行校正的荟萃分析（meta-analysis）中，共有两个基因座达到全基因组显著性水平：位于芳烃受体（aryl hydrocarbon receptor, AHR）附近的7p21区域（P=2.4×10^−19），以及位于细胞色素P450 1A1（cytochrome P450 1A1, CYP1A1）与细胞色素P450 1A2（cytochrome P450 1A2, CYP1A2）之间的15q24区域（P=5.2×10^−14）。芳烃受体与细胞色素P450 1A2这两个基因均为具备生物学合理性的候选基因：CYP1A2负责咖啡因的代谢，而AHR则可调控CYP1A2的表达。