The DOI matches its Crossref record; 36 of the 37 references it cites were found in a registry or an index.
Genome-Wide Meta-Analysis Identifies Regions on 7p21 (AHR) and 15q24 (CYP1A2) As Determinants of Habitual Caffeine Consumption
Open accessAbstract
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.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Recently, a genome-wide association study (GWAS) found a highly significant association between a variant on CYP1A2 and coffee intake48.”
From Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose–Response Meta-Analysis of Prospective Cohort Studies (2014) · cites this paper as [48]
In the citing paper
“However, this variant explains only a very small population variance.”
From Long-Term Coffee Consumption and Risk of Cardiovascular Disease: A Systematic Review and a Dose–Response Meta-Analysis of Prospective Cohort Studies (2014) · cites this paper as [48]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
KEGG: Kyoto Encyclopedia of Genes and Genomes
Kanehisa, M. (2000) · Nucleic Acids Research · doi:10.1093/nar/28.1.27 · Cited by 37,077
KEGG: Kyoto Encyclopedia of Genes and Genomes
Ogata, H., Goto, S., Sato, K., Fujibuchi, W., Bono, H., & Kanehisa, M. (1999) · Nucleic Acids Research · doi:10.1093/nar/27.1.29 · Cited by 31,232
Willett, W. C. (1998) · doi:10.1093/acprof:oso/9780195122978.001.0001 · Cited by 4,541
Reproducibility and validity of a semiquantitative food frequency questionnaire
WILLETT, W. C., SAMPSON, L., STAMPFER, M. J., ROSNER, B., BAIN, C., WITSCHI, J., HENNEKENS, C. H., & SPEIZER, F. E. (1985) · American Journal of Epidemiology · doi:10.1093/oxfordjournals.aje.a114086 · Cited by 4,274
Fredholm, B. B., Bättig, K., Holmén, J., Nehlig, A., & Zvartau, E. E. (1999) · Pharmacological Reviews · doi:10.1016/s0031-6997(24)01396-6 · Cited by 2,624 · cited 6×
“We further conducted 21 candidate gene analyses and found significant gene-based associations (Bonferroni corrected for the total number of human genes) between CYP2C9 (P = 0.023), and ADORA2A (P = 0.011) and caffeine intake in addition to CYP1A2 and AHR (Table 4).”
InfluentialA new multipoint method for genome-wide association studies by imputation of genotypes
Marchini, J., Howie, B., Myers, S., McVean, G., & Donnelly, P. (2007) · Nature Genetics · doi:10.1038/ng2088 · Cited by 2,609
Denison, M. S., & Nagy, S. R. (2003) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.43.100901.135828 · Cited by 1,895
Subar, A. F., Thompson, F. E., Kipnis, V., Midthune, D., Hurwitz, P. E., McNutt, S., McIntosh, A., & Rosenfeld, S. (2001) · American Journal of Epidemiology · doi:10.1093/aje/154.12.1089 · Cited by 1,401
Self-citationThe Molecular Receptive Ranges of Human TAS2R Bitter Taste Receptors
Meyerhof, W., Batram, C., Kühn, C., Brockhoff, A., Chudoba, E., Bufe, B., Appendino, G., & Behrens, M. (2009) · Chemical Senses · doi:10.1093/chemse/bjp092 · Cited by 1,146
Genome-wide meta-analyses identify multiple loci associated with smoking behavior
The Tobacco and Genetics Consortium (2010) · Nature Genetics · doi:10.1038/ng.571 · Cited by 1,098
Self-citationCoffee and Health: A Review of Recent Human Research
Higdon, J. V., & Frei, B. (2006) · Critical Reviews in Food Science and Nutrition · doi:10.1080/10408390500400009 · Cited by 1,090 · cited 1×
“Caffeine intake has been associated with pleotropic physiologic effects in relation to both detrimental and beneficial health outcomes [23].”
Feskanich, D., Rimm, E. B., Giovannucci, E. L., Colditz, G. A., Stampfer, M. J., Litin, L. B., & Willett, W. C. (1993) · Journal of the American Dietetic Association · doi:10.1016/0002-8223(93)91754-e · Cited by 1,070
Self-citationAggressiveness, hypoalgesia and high blood pressure in mice lacking the adenosine A2a receptor
Ledent, C. A., Vaugeois, J., Schiffmann, S. N., Pedrazzini, T., Yacoubi, M. E., Vanderhaeghen, J. J., Costentin, J., Heath, J. K., Vassart, G., & Parmentier, M. (1997) · Nature · doi:10.1038/41771 · Cited by 918
A Versatile Gene-Based Test for Genome-wide Association Studies
Liu, J. Z., McRae, A. F., Nyholt, D. R., Medland, S. E., Wray, N. R., Brown, K. M., Hayward, N. K., Montgomery, G. W., Visscher, P. M., Martin, N. G., et al. (2010) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2010.06.009 · Cited by 796
Pe'er, I., Yelensky, R., Altshuler, D., & Daly, M. J. (2008) · Genetic Epidemiology · doi:10.1002/gepi.20303 · Cited by 783
Food sources and intakes of caffeine in the diets of persons in the United States
Frary, C. D., Johnson, R. K., & Wang, M. Q. (2005) · Journal of the American Dietetic Association · doi:10.1016/j.jada.2004.10.027 · Cited by 681
Park, J.-H., Wacholder, S., Gail, M. H., Peters, U., Jacobs, K. B., Chanock, S. J., & Chatterjee, N. (2010) · Nature Genetics · doi:10.1038/ng.610 · Cited by 678
Self-citationAdenosine A2A, but not A1, receptors mediate the arousal effect of caffeine
Huang, Z.-L., Qu, W.-M., Eguchi, N., Chen, J.-F., Schwarzschild, M. A., Fredholm, B. B., Urade, Y., & Hayaishi, O. (2005) · Nature Neuroscience · doi:10.1038/nn1491 · Cited by 640
An Update on the Mechanisms of the Psychostimulant Effects of Caffeine
Ferré, S. (2008) · Journal of Neurochemistry · doi:10.1111/j.1471-4159.2007.05196.x · Cited by 440 · cited 1×
“Genetic association studies focused on candidate genes related to the pharmacokinetic and pharmacodynamic properties of caffeine have identified genes encoding cytochrome P-450 (CYP)1A2, as the primary enzyme involved in caffeine metabolism [3,4].”
ProbABEL package for genome-wide association analysis of imputed data
Aulchenko, Y. S., Struchalin, M. V., & van Duijn, C. M. (2010) · BMC Bioinformatics · doi:10.1186/1471-2105-11-134 · Cited by 400
Kot, M., & Daniel, W. A. (2008) · Biochemical Pharmacology · doi:10.1016/j.bcp.2008.05.025 · Cited by 389
Heterogeneity in Meta-Analyses of Genome-Wide Association Investigations
Ioannidis, J. P. A., Patsopoulos, N. A., & Εvangelou, Ε. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000841 · Cited by 338
Genetics of caffeine consumption and responses to caffeine
Yang, A., Palmer, A. A., & de Wit, H. (2010) · Psychopharmacology · doi:10.1007/s00213-010-1900-1 · Cited by 330
Subar, A. F. (2000) · American Journal of Epidemiology · doi:10.1093/aje/152.3.279 · Cited by 304
Self-citationZhou, S.-F., Wang, B., Yang, L.-P., & Liu, J. (2009) · Drug Metabolism Reviews · doi:10.3109/03602530903286476 · Cited by 270
Gunes, A., & Dahl, M. (2008) · Pharmacogenomics · doi:10.2217/14622416.9.5.625 · Cited by 257
Genetic polymorphism of the adenosine A2A receptor is associated with habitual caffeine consumption
Cornelis, M. C., El‐Sohemy, A., & Campos, H. (2007) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/86.1.240 · Cited by 231
Self-citationRogers, P. J., Hohoff, C., Heatherley, S. V., Mullings, E. L., Maxfield, P. J., Evershed, R. P., Deckert, J., & Nutt, D. J. (2010) · Neuropsychopharmacology · doi:10.1038/npp.2010.71 · Cited by 212
Ridker, P. M., Chasman, D. I., Zee, R. Y. L., Parker, A. N., Rose, L. M., Cook, N. R., Buring, J. E., & for the Women’s Genome Health Study Working Group (2007) · Clinical Chemistry · doi:10.1373/clinchem.2007.099366 · Cited by 169
Self-citationPolymorphisms in the human AH receptor
Harper, P. A., Wong, J. M. Y., Lam, M. S. M., & Okey, A. B. (2002) · Chemico-Biological Interactions · doi:10.1016/s0009-2797(02)00071-6 · Cited by 168
Organization of the CYP1A cluster on human chromosome 15: implications for gene regulation
Corchero, J., Pimprale, S., Kimura, S., & Gonzalez, F. J. (2001) · Pharmacogenetics · doi:10.1097/00008571-200102000-00001 · Cited by 125
Ueda, R., Iketaki, H., Nagata, K., Kimura, S., Gonzalez, F. J., Kusano, K., Yoshimura, T., & Yamazoe, Y. (2006) · Molecular Pharmacology · doi:10.1124/mol.105.021220 · Cited by 97
Reliability of a food frequency questionnaire by ethnicity, gender, age and education
Stevens, J., Metcalf, P., Dennis, B. H., Tell, G. S., Shimakawa, T., & Folsom, A. R. (1996) · Nutrition Research · doi:10.1016/0271-5317(96)00064-4 · Cited by 90
Discovery Properties of Genome-wide Association Signals From Cumulatively Combined Data Sets
Pereira, T., Patsopoulos, N. A., Salanti, G., & Ioannidis, J. P. A. (2009) · American Journal of Epidemiology · doi:10.1093/aje/kwp262 · Cited by 62
Jorge-Nebert, L. F., Jiang, Z., Chakraborty, R., Watson, J., Li, J., McGarvey, S. T., Deka, R., & Nebert, D. W. (2009) · Human Mutation · doi:10.1002/humu.21132 · Cited by 61
Luciano, M., Kirk, K. M., Heath, A. C., & Martin, N. G. (2005) · Addiction · doi:10.1111/j.1360-0443.2005.01223.x · Cited by 52
Flagged first, then by citations
1 of the 37 references couldn’t be matched to a known paper.
Research works printed but not linked: 1
- Y Li, 2006, Mach 1.0: Rapid haplotype reconstruction and missing genotype inference., Am J Hum Genet, S79, 2290
Cited by
Sorted by citations
Zanger, U. M., & Schwab, M. (2013) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2012.12.007 · Cited by 4,169
“Several genome-wide association studies (GWAS) and GWAS meta-analyses involving many thousands of subjects identified SNPs in the regulatory region of the CYP1A locus (rs2472304, rs2472297) as well as SNPs in the AhR gene regulatory region (rs4410790, rs6968865) along with genes related to addictive behavior to be ass…”
BackgroundInternational society of sports nutrition position stand: caffeine and performance
Goldstein, E. R., Ziegenfuss, T., Kalman, D., Kreider, R., Campbell, B., Wilborn, C., Taylor, L., Willoughby, D., Stout, J., Graves, B. S., et al. (2010) · Journal of the International Society of Sports Nutrition · doi:10.1186/1550-2783-7-5 · Cited by 686
International Society of Sports Nutrition Position Stand: Caffeine and Exercise Performance
Guest, N. S., VanDusseldorp, T. A., Nelson, M. T., Grgic, J., Schoenfeld, B. J., Jenkins, N. D. M., Arent, S. M., Antonio, J., Stout, J. R., Trexler, E. T., et al. (2021) · Journal of the International Society of Sports Nutrition · doi:10.1186/s12970-020-00383-4 · Cited by 665
Interindividual Differences in Caffeine Metabolism and Factors Driving Caffeine Consumption
Nehlig, A. (2018) · Pharmacological Reviews · doi:10.1124/pr.117.014407 · Cited by 632
Sugar-Sweetened Beverages and Genetic Risk of Obesity
Qi, Q., Chu, A. Y., Kang, J., Jensen, M. K., Curhan, G. C., Pasquale, L. R., Ridker, P. M., Hunter, D. J., Willett, W. C., Rimm, E. B., et al. (2012) · New England Journal of Medicine · doi:10.1056/nejmoa1203039 · Cited by 609
Self-citation
Metadata
- Authors
- Cornelis, M. C., Monda, K. L., Yu, K., Paynter, N., Azzato, E. M., Bennett, S. N., Berndt, S. I., Boerwinkle, E., Chanock, S., Chatterjee, N., Couper, D., Curhan, G., Heiss, G., Hu, F. B., Hunter, D. J., Jacobs, K., Jensen, M. K., Kraft, P., Landi, M. T., Nettleton, J. A., Purdue, M. P., Rajaraman, P., Rimm, E. B., Rose, L. M., Rothman, N., Silverman, D., Stolzenberg-Solomon, R., Subar, A., Yeager, M., Chasman, D. I., van Dam, R. M., & Caporaso, N. E.
- Affiliations
- Harvard University (US)
- University of North Carolina at Chapel Hill (US)
- National Institutes of Health (US)
- Brigham and Women's Hospital (US)
- University of Washington (US)
- The University of Texas Health Science Center at Houston (US)
- National University of Singapore (SG)
- Corresponding author
- Chasman, Daniel I.
- van Dam, Rob M.
- Caporaso, Neil E.
- ORCID
- Cornelis, Marilyn C.
- Yu, Kai
- Paynter, Nina
- Azzato, Elizabeth M.
- Berndt, Sonja I.
- Boerwinkle, Eric
- Chanock, Stephen
- Chatterjee, Nilanjan
- Couper, David
- Curhan, Gary
- Heiss, Gerardo
- Hu, Frank B.
- Jacobs, Kevin
- Jensen, Majken K.
- Kraft, Peter
- Landi, Maria Teresa
- Purdue, Mark P.
- Rajaraman, Preetha
- Rimm, Eric B.
- Rose, Lynda M.
- Rothman, Nathaniel
- Silverman, Debra
- Yeager, Meredith
- Chasman, Daniel I.
- van Dam, Rob M.
- Caporaso, Neil E.
- Venue
- PLoS Genetics
- Publisher
- Public Library of Science (PLoS)
- Published
- 2011-04-07
- Volume
- 7
- Issue
- 4
- Pages
- e1002033
- ISSN
- 1553-7390 (ISSN-L)
- 1553-7404
- PMC
- PMC3071630
- OpenAlex
- W2147245308
- Cited by
- 228
- References
- 37
- Citations by year
- 2026: 8 · 2025: 8 · 2024: 10 · 2023: 10 · 2022: 8 · 2021: 13 · 2020: 21 · 2019: 15 · 2018: 20 · 2017: 15 · 2016: 21 · 2015: 15 · 2014: 20 · 2013: 18 · 2012: 18
- FWCI
- 14.76
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- PLoS Genetics (publishedVersion, public-domain)
- Europe PMC (PubMed Central) (publishedVersion, public-domain)
- PubMed Central (publishedVersion, public-domain)
- PubMed (publishedVersion)
- Carolina Digital Repository (University of North Carolina at Chapel Hill) (submittedVersion)
- Digital Access to Scholarship at Harvard (DASH) (Harvard University) (submittedVersion, cc-by)
- National University of Singapore (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Figshare (submittedVersion, cc-by)
- UNC Libraries
- Funders
- U.S. Department of Health and Human Services (R01HL086694, U10AA008401, U01HG004438, R01HL087641, R01HL59367, U01HG004729)
- Donald W. Reynolds Foundation
- Amgen
- Division of Cancer Prevention, National Cancer Institute (CA55075)
- Johns Hopkins University (N01-HC-55020, HHSN268200782096C, U01HG004438)
- Broad Institute
- Fondation Leducq
- National Institutes of Health (HSN268200625226C, n01hc55021-47-0-1, n01hc55020-39-0-0, n01hc55016-37-0-0, n01hc055022-024, 5u01hg004423-02, n01hc55019-35-0-1, 5p01dk070756-05, n01hc55018-38-0-1, 5r01hl043851-10, HHSN268200782096C, N01-HC55020, N01-HC-55021, N01-HC-55019, N01-HC-55022, N01-HC55016, N01-HC55018, CA55075, CA54281, CA63464, N01-HC-55015, HL69757, n01hc55015-48-0-1)
- U.S. Public Health Service (AHG006033)
- Canadian Institutes of Health Research (U10AA008401, CA63464, CA54281)
- National Institute on Alcohol Abuse and Alcoholism (HHSN268200782096C, U10AA008401)
- National Heart, Lung, and Blood Institute (N01-HC55022, HC-55016, N01 HC055016, N01-HC-55018, R01HL087641, R01HL59367 and R01HL086694, HL043851, N01 HC 55020, R01‐HL043851, HC-55021, HC-55018, N01 HC 55019, R01 HL-59367, U19HL069757, HC-55022, N01 HC055020, R01HL035464, HC-55019, N01-HC, N01 HC055018, HC-55015, U01HL069757, HC-55020, N01-HC55016, R01HL087641, N01 HC055022, HL 69757, R01HL059367, HL35464, HHSN268200782096C, N01 HC055019, CA55075, N01‐HC‐55015, N01-HC55021, CA047988, N01 HC055021, N01 HC055015, R01HL086694)
- National Institute on Drug Abuse (01DA013423, R01DA013423, HHSN268200782096C)
- National Human Genome Research Institute (U01HG004735, U01-HG004423, U01HG004726, U01HG04424, U01HG004422, U01HG004738, U01HG004399, U01HG004402, U01HG004728, U01HG004415, U01HG004446, U01HG004729, U01HG004424, U01HG004438, U01HG004436, 01HG004735, HHSN268200782096C)
- National Cancer Institute (R01CA040356, CA63464, CA136792, U01CA063464, CA-55075, R37CA054281, CA-40356, CA98233, P01CA087969, R01CA054281, P01CA089392, CA 047988, R01CA063464, CA 54281, U01 CA 98233, P01CA055075, U01CA098233, R01CA047988, U01CA136792, Z01CP010200)
- National Institute of Diabetes and Digestive and Kidney Diseases (P01-DK-070756, R01DK058845, N01-HC-55016, N01-HC-55018, N01-HC-55021, N01-HC-55020, N01-HC-55015, 5P01DK070756, N01-HC-55019, N01-HC-55022)
- National Institute of Dental and Craniofacial Research (U01DE018993, U01DE018903, HHSN268200782096C)
- National Center for Research Resources (UL1RR025005)
- Topics
- Health Sciences › Medicine › Pharmacology (medical) › Coffee research and impacts
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- habitual caffeine consumption, caffeine consumption, CYP1A1, caffeine metabolism, gene expression regulation
- MeSH terms
- Adult, Aged, Caffeine, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 7, Drinking Behavior, Female, Genotype, Humans, Male, Middle Aged, Quality Control, Sex Factors, United States, Receptors, Aryl Hydrocarbon, Cytochrome P-450 CYP1A2, Polymorphism, Single Nucleotide, White People, Genome-Wide Association Study
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
