Phenotype refinement strengthens the association of AHR and CYP1A1 genotype with caffeine consumption.
Phenotype refinement strengthens the association of AHR and CYP1A1 genotype with caffeine consumption.
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DOI：
10.1371/journal.pone.0103448
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发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Munafò MR
中科院分区：
文献类型：
--
作者：
McMahon G;Taylor AE;Davey Smith G;Munafò MR
两个基因位点，一个位于细胞色素P450 1A1 （CYP1A1）和1A2 （CYP1A2）基因区域（rs2472297），一个靠近芳烃受体（AHR）基因（rs6968865），与习惯性咖啡因摄入有关。我们试图确定是否对咖啡因摄入进行更精细和全面的评估会提供更有力的证据，以及包含这两种变体的联合等位基因评分是否会进一步加强这种联系。我们使用了来自英国纵向出生队列——雅芳父母与儿童纵向研究的4460至7520名妇女的数据。关于咖啡、茶和可乐消费（包括不含咖啡因的饮料的消费）的自我报告数据在多个时间点都是可用的。这两种基因型分别与咖啡因的总摄入量、咖啡和茶的摄入量有关。这与可乐的摄入量没有关联，可能是由于这个样本的摄入量很低。研究结果也与饮用不含咖啡因的饮料没有关联，这表明观察到的关联很可能是通过咖啡因介导的。当使用联合等位基因评分时，这种关联得到加强，占表型方差的1.28%。这与观察关联的潜在混杂因素无关。联合等位基因评分说明了咖啡因摄入中足够的表型变异，这可能在孟德尔随机化研究中有用。因此，未来的研究可能能够利用这种联合等位基因评分来探索习惯性摄入咖啡因对健康结果的因果影响。
Two genetic loci, one in the cytochrome P450 1A1 (CYP1A1) and 1A2 (CYP1A2) gene region (rs2472297) and one near the aryl-hydrocarbon receptor (AHR) gene (rs6968865), have been associated with habitual caffeine consumption. We sought to establish whether a more refined and comprehensive assessment of caffeine consumption would provide stronger evidence of association, and whether a combined allelic score comprising these two variants would further strengthen the association. We used data from between 4,460 and 7,520 women in the Avon Longitudinal Study of Parents and Children, a longitudinal birth cohort based in the United Kingdom. Self-report data on coffee, tea and cola consumption (including consumption of decaffeinated drinks) were available at multiple time points. Both genotypes were individually associated with total caffeine consumption, and with coffee and tea consumption. There was no association with cola consumption, possibly due to low levels of consumption in this sample. There was also no association with measures of decaffeinated drink consumption, indicating that the observed association is most likely mediated via caffeine. The association was strengthened when a combined allelic score was used, accounting for up to 1.28% of phenotypic variance. This was not associated with potential confounders of observational association. A combined allelic score accounts for sufficient phenotypic variance in caffeine consumption that this may be useful in Mendelian randomization studies. Future studies may therefore be able to use this combined allelic score to explore causal effects of habitual caffeine consumption on health outcomes.
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DOI：
10.1056/nejmoa1112010
发表时间：
2012-05-17
期刊：
The New England journal of medicine
影响因子：
--
作者：
Freedman ND;Park Y;Abnet CC;Hollenbeck AR;Sinha R
通讯作者：
Sinha R
影响因子：
7.7
作者：
Freathy RM;Kazeem GR;Morris RW;Johnson PC;Paternoster L;Ebrahim S;Hattersley AT;Hill A;Hingorani AD;Holst C;Jefferis BJ;Kring SI;Mooser V;Padmanabhan S;Preisig M;Ring SM;Sattar N;Upton MN;Vollenweider P;Waeber G;Sørensen TI;Frayling TM;Watt G;Lawlor DA;Whincup PH;Tozzi F;Davey Smith G;Munafò M
通讯作者：
Munafò M
影响因子：
7.1
作者：
Josse, Andrea R.;Da Costa, Laura A.;El-Sohemy, Ahmed
通讯作者：
El-Sohemy, Ahmed
影响因子：
3.8
作者：
CONTERIO, F;CHIARELLI, B
通讯作者：
CHIARELLI, B
影响因子：
56.9
作者：
Frayling, Timothy M.;Timpson, Nicholas J.;McCarthy, Mark I.
通讯作者：
McCarthy, Mark I.