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Genome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.

TitleGenome-wide meta-analysis identifies regions on 7p21 (AHR) and 15q24 (CYP1A2) as determinants of habitual caffeine consumption.
Publication TypeJournal Article
Year of Publication2011
AuthorsCornelis MC, Monda KL, Yu K, Paynter N, Azzato EM, Bennett SN, Berndt SI, Boerwinkle E, Chanock S, Chatterjee N, Couper D, Curhan G, Heiss G, Hu FB, Hunter DJ, Jacobs K, Jensen MK, Kraft P, Landi M T, Nettleton JA, Purdue MP, Rajaraman P, Rimm EB, Rose LM, Rothman N, Silverman D, Stolzenberg-Solomon R, Subar A, Yeager M, Chasman DI, van Dam RM, Caporaso NE
JournalPLoS Genet
Volume7
Issue4
Paginatione1002033
Date Published2011 Apr
ISSN1553-7404
KeywordsAdult, Aged, Caffeine, Chromosomes, Human, Pair 15, Chromosomes, Human, Pair 7, Cytochrome P-450 CYP1A2, Drinking Behavior, European Continental Ancestry Group, Female, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Quality Control, Receptors, Aryl Hydrocarbon, Sex Factors, United States
Abstract

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.
DOI10.1371/journal.pgen.1002033
Alternate JournalPLoS Genet
PubMed ID21490707
PubMed Central IDPMC3071630
Grant ListR01HL59367 / HL / NHLBI NIH HHS / United States
R01 HL086694 / HL / NHLBI NIH HHS / United States
Z01 CP010200 / / Intramural NIH HHS / United States
U01 HG004729 / HG / NHGRI NIH HHS / United States
R01 CA063464 / CA / NCI NIH HHS / United States
U01 HG004735 / HG / NHGRI NIH HHS / United States
U01 CA136792 / CA / NCI NIH HHS / United States
CA136792 / CA / NCI NIH HHS / United States
N01HC55020 / HL / NHLBI NIH HHS / United States
U01HG004446 / HG / NHGRI NIH HHS / United States
UL1RR025005 / RR / NCRR NIH HHS / United States
CA54281 / CA / NCI NIH HHS / United States
P01CA089392 / CA / NCI NIH HHS / United States
U01HG004726 / HG / NHGRI NIH HHS / United States
U01HG004438 / HG / NHGRI NIH HHS / United States
R01 DK058845 / DK / NIDDK NIH HHS / United States
U01 HG004728 / HG / NHGRI NIH HHS / United States
U01 HG004438 / HG / NHGRI NIH HHS / United States
U10AA008401 / AA / NIAAA NIH HHS / United States
P01CA087969 / CA / NCI NIH HHS / United States
U01 HG004446 / HG / NHGRI NIH HHS / United States
N01HC55018 / HL / NHLBI NIH HHS / United States
UL1 RR025005 / RR / NCRR NIH HHS / United States
AHG006033 / / PHS HHS / United States
U01HG004738 / HG / NHGRI NIH HHS / United States
P01 CA087969 / CA / NCI NIH HHS / United States
HL 043851 / HL / NHLBI NIH HHS / United States
P01CA055075 / CA / NCI NIH HHS / United States
U01-CA98233 / CA / NCI NIH HHS / United States
HL69757 / HL / NHLBI NIH HHS / United States
N01-HC-55022 / HC / NHLBI NIH HHS / United States
U01HG004415 / HG / NHGRI NIH HHS / United States
R01 HL059367 / HL / NHLBI NIH HHS / United States
R01 HL043851 / HL / NHLBI NIH HHS / United States
U01 DE018993 / DE / NIDCR NIH HHS / United States
P01 CA055075 / CA / NCI NIH HHS / United States
N01-HC-55016 / HC / NHLBI NIH HHS / United States
P01 DK070756 / DK / NIDDK NIH HHS / United States
P01 CA089392 / CA / NCI NIH HHS / United States
/ CAPMC / CIHR / Canada
U01HG004728 / HG / NHGRI NIH HHS / United States
U01HG004399 / HG / NHGRI NIH HHS / United States
5P01DK070756 / DK / NIDDK NIH HHS / United States
N01-HC-55021 / HC / NHLBI NIH HHS / United States
U01 HG004402 / HG / NHGRI NIH HHS / United States
CA55075 / CA / NCI NIH HHS / United States
U01 HG004424 / HG / NHGRI NIH HHS / United States
N01HC55022 / HL / NHLBI NIH HHS / United States
01HG004735 / HG / NHGRI NIH HHS / United States
N01HC55015 / HL / NHLBI NIH HHS / United States
U01 HG004415 / HG / NHGRI NIH HHS / United States
U01HG004402 / HG / NHGRI NIH HHS / United States
U01HG004422 / HG / NHGRI NIH HHS / United States
CA 047988 / CA / NCI NIH HHS / United States
CA63464 / CA / NCI NIH HHS / United States
HHSN268200782096C / HG / NHGRI NIH HHS / United States
N01-HC-55019 / HC / NHLBI NIH HHS / United States
U01 HG004422 / HG / NHGRI NIH HHS / United States
U01HG04424 / HG / NHGRI NIH HHS / United States
R01HL087641 / HL / NHLBI NIH HHS / United States
N01-HC-55015 / HC / NHLBI NIH HHS / United States
R01 DA013423 / DA / NIDA NIH HHS / United States
U01DE018993 / DE / NIDCR NIH HHS / United States
U01HG004423 / HG / NHGRI NIH HHS / United States
N01-HC-55020 / HC / NHLBI NIH HHS / United States
N01HC55016 / HL / NHLBI NIH HHS / United States
HL35464 / HL / NHLBI NIH HHS / United States
R01 CA054281 / CA / NCI NIH HHS / United States
U01 CA098233 / CA / NCI NIH HHS / United States
R01DK058845 / DK / NIDDK NIH HHS / United States
U01DE018903 / DE / NIDCR NIH HHS / United States
U01 CA063464 / CA / NCI NIH HHS / United States
R01 CA047988 / CA / NCI NIH HHS / United States
U01HG004436 / HG / NHGRI NIH HHS / United States
U01HG004729 / HG / NHGRI NIH HHS / United States
01DA013423 / DA / NIDA NIH HHS / United States
N01HC55019 / HL / NHLBI NIH HHS / United States
U01 DE018903 / DE / NIDCR NIH HHS / United States
U01 HG004436 / HG / NHGRI NIH HHS / United States
U19 HL069757 / HL / NHLBI NIH HHS / United States
R01 HL035464 / HL / NHLBI NIH HHS / United States
U01 HG004738 / HG / NHGRI NIH HHS / United States
U10 AA008401 / AA / NIAAA NIH HHS / United States
U01 HG004423 / HG / NHGRI NIH HHS / United States
R01 CA040356 / CA / NCI NIH HHS / United States
N01-HC-55018 / HC / NHLBI NIH HHS / United States
N01HC55021 / HL / NHLBI NIH HHS / United States
R01 HL087641 / HL / NHLBI NIH HHS / United States
U01 HL069757 / HL / NHLBI NIH HHS / United States
R37 CA054281 / CA / NCI NIH HHS / United States
U01 HG004399 / HG / NHGRI NIH HHS / United States
R01HL086694 / HL / NHLBI NIH HHS / United States
CA 40356 / CA / NCI NIH HHS / United States
U01 HG004726 / HG / NHGRI NIH HHS / United States