Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.
Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.
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DOI：
10.1371/journal.pgen.1002033
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发表时间：
2011-04
期刊：
影响因子：
4.5
通讯作者：
Caporaso NE
中科院分区：
文献类型：
--
作者：
Cornelis MC;Monda KL;Yu K;Paynter N;Azzato EM;Bennett SN;Berndt SI;Boerwinkle E;Chanock S;Chatterjee N;Couper D;Curhan G;Heiss G;Hu FB;Hunter DJ;Jacobs K;Jensen MK;Kraft P;Landi MT;Nettleton JA;Purdue MP;Rajaraman P;Rimm EB;Rose LM;Rothman N;Silverman D;Stolzenberg-Solomon R;Subar A;Yeager M;Chasman DI;van Dam RM;Caporaso NE
我们报告了第一项与习惯性咖啡因摄入的全基因组关联研究。我们根据美国境内5项基于人群的研究纳入了47,341名欧洲人后裔。在一项调整了年龄、性别、吸烟和群体变异特征向量的荟萃分析中，两个基因座在CYP1A1和CYP1A2之间具有全基因组意义：靠近AHR的7p21 （P = 2.4×10−19）和位于CYP1A1和CYP1A2之间的15q24 （P = 5.2×10−14）。AHR和CYP1A2基因都是生物学上合理的候选基因，因为CYP1A2代谢咖啡因，而AHR调节CYP1A2。咖啡因是世界上消费最广泛的精神活性物质。虽然人口统计和社会因素与习惯性摄入咖啡因有关，但双胞胎研究报告称，遗传因素占很大一部分。通过对超过40,000名参与者的人类基因组进行全面搜索，我们发现了两个与习惯性咖啡因摄入相关的位点：第一个靠近AHR，第二个位于CYP1A1和CYP1A2之间。AHR和CYP1A2基因都是生物学上合理的候选基因，因为CYP1A2代谢咖啡因，而AHR调节CYP1A2。咖啡因摄入与多种生理效应以及有害和有益的健康结果有关。了解咖啡因摄入的遗传决定因素可能有助于深入了解潜在的机制，并可能为更全面地研究咖啡因对健康的潜在影响提供方法。
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. Caffeine is the most widely consumed psychoactive substance in the world. Although demographic and social factors have been linked to habitual caffeine consumption, twin studies report a large heritable component. Through a comprehensive search of the human genome involving over 40,000 participants, we discovered two loci associated with habitual caffeine consumption: the first near AHR and the second between CYP1A1 and CYP1A2. Both the AHR and CYP1A2 genes are biologically plausible candidates, as CYP1A2 metabolizes caffeine and AHR regulates CYP1A2. Caffeine intake has been associated with manifold physiologic effects and both detrimental and beneficial health outcomes. Knowledge of the genetic determinants of caffeine intake may provide insight into underlying mechanisms and may provide ways to study the potential health effects of caffeine more comprehensively.
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影响因子：
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