Two genes in which variation affects intake of caffeine, the most widely consumed stimulant in the world, have been discovered. A team of investigators from the National Cancer Institute, Harvard School of Public Health, Brigham and Women's Hospital, and the University of North Carolina at Chapel Hill examined genetic variation across the entire genome of more than 47,000 individuals from the U.S., as described in the open-access journal PLoS Genetics.

The genes identified were CYP1A2, which has previously been implicated in the metabolism of caffeine, and AHR, involved in the regulation of CYP1A2. Individuals with the highest-consumption genotype for either gene consumed ~40 mg more caffeine than those with the lowest-consumption genotype, equivalent to the amount of 1/3 cup of caffeinated coffee, or 1 can of cola.

Caffeine is implicated in numerous physiological and medical conditions; it affects sleep patterns, energy levels, mood, and mental and physical performance. The identification of genes that have an impact on daily consumption offers opportunities to better understand these conditions. Further exploration of the identified genetic variants may provide insight into the speed of caffeine metabolism, how long caffeine circulates in the blood, or how strong the physiological effects of consuming a given amount of caffeine are.

Apart from smoking, genetic determinants of lifestyle behaviors have generally not been consistently described. This study is among the first to examine the entire genome for a relationship between genetics and caffeine intake, a lifestyle behavior relevant to over 90% of U.S. adults. The study's success also suggests that additional genetic determinants of dietary and lifestyle behaviors may be identified in the future using a similar genome-based research strategy.

Financial Disclosure: ARIC is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute (NHLBI) contracts N01-HC-55015, N01-HC-55016, N01-HC-55018, N01-HC-55019, N01-HC-55020, N01-HC-55021, N01-HC-55022, R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HSN268200625226C. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. The NHS Breast Cancer GW scan was performed as part of the Cancer Genetic Markers of Susceptibility initiative of the NCI. We particularly acknowledge the contributions of R. Hoover, A. Hutchinson, K. Jacobs, and G. Thomas. The current research is supported by CA 40356 and U01-CA98233 from the NCI. The NHS/HPFS type 2 diabetes GWAS (U01HG004399) is a component of a collaborative project that includes 13 other GWAS funded as part of the Gene Environment-Association Studies (GENEVA) under the NIH Genes, Environment, and Health Initiative (GEI) (U01HG004738, U01HG004422, U01HG004402, U01HG004729, U01HG004726, 01HG004735, U01HG004415, U01HG004436, U01HG004423, U01HG004728, AHG006033) with additional support from individual NIH Institutes (NIDCR: U01DE018993, U01DE018903; NIAAA: U10AA008401; NIDA: P01CA089392, 01DA013423; NCI: CA63464, CA54281, CA136792, Z01CP010200). Assistance with genotype cleaning and general study coordination, was provided by the GENEVA Coordinating Center (U01HG004446). Assistance with data cleaning was provided by the NCBI. Genotyping was performed at the Broad Institute of MIT and Harvard, with funding support from the NIH GEI (U01HG04424), and Johns Hopkins University Center for Inherited Disease Research, with support from the NIH GEI (U01HG004438) and the NIH contract "High throughput genotyping for studying the genetic contributions to human disease" (HHSN268200782096C). Additional funding for the current research was provided by the NCI (P01CA087969, P01CA055075) and the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK, R01DK058845). The NHS/HPFS CHD GWAS was supported by HL35464 and CA55075 from the NIH with additional support for genotyping from Merck/Rosetta Research Laboratories, North Wales, PA. The NHS/HPFS Kidney GWAS was supported by NIDDK: 5P01DK070756. PLCO was supported the Intramural Research Program of the Division of Cancer Epidemiology and Genetics and by contracts from the Division of Cancer Prevention, National Cancer Institute, NIH, DHHS. The WGHS is supported by HL 043851 and HL69757 from the NHLBI and CA 047988 from the NCI, the Donald W. Reynolds Foundation, and the Fondation Leducq, with collaborative scientific support and funding for genotyping provided by Amgen. Marilyn C. Cornelis is a recipient of a Canadian Institutes of Health Research Fellowship. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Competing Interests: The authors have declared that no competing interests exist.

Citation: "Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) As Determinants of Habitual Caffeine Consumption"
Cornelis MC, Monda KL, Yu K, Paynter N, Azzato EM, et al. (2011)
PLoS Genet 7(4): e1002033. doi:10.1371/journal.pgen.1002033

Source:
PLoS Genetics