Phenotype refinement strengthens the association of AHR and CYP1A1 genotype with caffeine consumption

• Published in: PloS one 2014-07, Vol.9 (7), p.e103448-e103448
• Main Authors: McMahon, George, Taylor, Amy E, Davey Smith, George, Munafò, Marcus R
• Format: Article
• Language: English
• Subjects: Adult; Alcohol; Alcohol use; Alzheimer's disease; Alzheimers disease; Aromatic compounds; Associations; Basic Helix-Loop-Helix Transcription Factors - genetics; Beverages; Body mass index; Caffeine; Caffeine - metabolism; Cancer; Children; Coffee; Coffee (Beverage); Consumption; Correlation analysis; Councils; CYP1A2 protein; Cytochrome; Cytochrome P-450; Cytochrome P-450 CYP1A1 - genetics; Cytochrome P450; Data dictionaries; Drinking Behavior; Epidemiology; Ethics; Experimental psychology; Female; Genes; Genetic aspects; Genetic Variation; Genotype; Genotypes; Health risk assessment; Humans; Hypertension; Life Style; Longitudinal Studies; Medical research; Medicine and Health Sciences; Parents; Phenotype; Phenotypes; Polymorphism, Single Nucleotide; Pregnancy; Prostate; Receptors, Aryl Hydrocarbon - genetics; Self Report; Smoking; Studies; Surveys and Questionnaires; Tea
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0103448

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.