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.
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“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]
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“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]
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1 of the 37 references couldn’t be matched to a known paper.
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Sex Differences in Cardiovascular Drug Response
Rodenburg, E. M. (2012) · RePub (Erasmus University Rotterdam)
Bogl, L. H. (2014) · Työväentutkimus Vuosikirja
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Ghoch, M. E., & Shamieh, S. E. (2020) · MDPI eBooks · doi:10.3390/books978-3-03943-241-7
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Bastian, J. R. (2016)
Virtanen, H. (2017) · Libraries and Cultural Resources (University of Calgary) · doi:10.11575/prism/24696
Genetic Testing, Genetic Variation, and Genetic Susceptibility
de Maturana, E. L., & Malats, N. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-809939-1.00033-3
Ong, J. (2019) · The University of Queensland · doi:10.14264/uql.2019.880
Allyn-Feuer, A. (2018) · Deep Blue (University of Michigan)
Is there utility to genetic information in elite sport?
Pickering, C. (2020) · CLOK (University of Central Lancashire) · doi:10.13140/rg.2.2.25902.54081 · Cited by 1
(2014) · CRC Press eBooks · doi:10.1201/b17423-69
Cotton, S. (2011) · Chapman & Hall/CRC eBooks · doi:10.1201/b11443-16
Hirbo, J. B., Pasutto, F., Gamazon, E. R., Evans, P. D., Pawar, P. P., Berner, D., Sealock, J., Tao, R., Straub, P., Konkashbaev, A. I., et al. (2020) · doi:10.21203/rs.3.rs-53203/v1
Denden, S., Sellami, M. H., Kibech, R., Khelil, A. H., & Hamdaoui, M. H. (2023) · Bulletin of the National Research Centre/Bulletin of the National Research Center · doi:10.1186/s42269-023-00978-2
AHR rs4410790 genotype and IgG levels: Effect modification by lifestyle factors
Khil, J., Kim, S., Lee, M., Gil, H., Kang, S., Lee, D. H., Kwon, Y., & Keum, N. (2023) · PLoS ONE · doi:10.1371/journal.pone.0290700
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BackgroundResultGenetic methods to evaluate evidence for causal effect of coffee on health
Pham, K., & Hyppönen, E. (2024) · Elsevier eBooks · doi:10.1016/b978-0-443-13868-3.00040-5
Djordjevic, N. (2025) · Royal Society of Chemistry eBooks · doi:10.1039/9781839166853-00341
Söderholm, S., Ulander, M., Toma, V. W., Kaufmann, S., Qiao, X., Berglind, D., Calling, S., Daka, B., Grote, L., Martinell, M., et al. (2026) · PLoS ONE · doi:10.1371/journal.pone.0344479
“The most significantly associated variants are found to affect the Aryl-Hydrocarbon Receptor ( AHR ) and the Cytochrome P450 Family 1 Subfamily A Member 1 and 2 ( CYP1A1 and CYP1A2 ) genetic loci [6–8].”
Qiao, X., Toma, V. W., Wang, J., Herráiz-Adillo, Á., Söderholm, S., Berglind, D., Calling, S., Daka, B., Martinell, M., Bergman, F., et al. (2026) · Scientific Reports · doi:10.1038/s41598-026-44122-2
“The SNPs identified in GWAS highlighted genetic regions involved in caffeine metabolism, such as CYP1A2 (15q24) and AHR (7p21) 20,21 .”
Influence de polymorphismes génétiques sur le sommeil et l'efficacité de la caféine
Erblang, M. (2020) · theses.fr (ABES) · doi:10.70675/10d39c5czed91z47dez802cz926b956f3874
Bae, J. H., & Kang, H. (2026) · Nutrients · doi:10.3390/nu18091319
“After applying all clinical exclusions and genomic quality control steps, the final analytic sample for the GWAS consisted of 12,098 women and 7555 men (total n = 19,653) [21,22].”
Attard, E., Ammendolia, I., Calapai, F., & Calapai, G. (2026) · Forensic Sciences · doi:10.3390/forensicsci6020051
Obesity Polygenic Risk and Healthy Lifestyle Interactions on Weight Trajectories in Women and Men
Ghosh, A., Lau, M., Fernandes, A., Cade, B. E., Karlson, E. W., Redline, S. S., Saxena, R., Huang, T., & Dashti, H. S. (2026) · Journal of the American Heart Association · doi:10.1161/jaha.126.049396
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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
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