title: Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption.
abstract: Coffee is the most commonly used stimulant and caffeine is its main psychoactive ingredient. The heritability of coffee consumption has been estimated at around 50%. We performed a meta-analysis of four genome-wide association studies of coffee consumption among coffee drinkers from Iceland (n = 2680), The Netherlands (n = 2791), the Sorbs Slavonic population isolate in Germany (n = 771) and the USA (n = 369) using both directly genotyped and imputed single nucleotide polymorphisms (SNPs) (2.5 million SNPs). SNPs at the two most significant loci were also genotyped in a sample set from Iceland (n = 2430) and a Danish sample set consisting of pregnant women (n = 1620). Combining all data, two sequence variants significantly associated with increased coffee consumption: rs2472297-T located between CYP1A1 and CYP1A2 at 15q24 (P = 5.4 · 10(-14)) and rs6968865-T near aryl hydrocarbon receptor (AHR) at 7p21 (P = 2.3 · 10(-11)). An effect of ∼0.2 cups a day per allele was observed for both SNPs. CYP1A2 is the main caffeine metabolizing enzyme and is also involved in drug metabolism. AHR detects xenobiotics, such as polycyclic aryl hydrocarbons found in roasted coffee, and induces transcription of CYP1A1 and CYP1A2. The association of these SNPs with coffee consumption was present in both smokers and non-smokers.
authors.affiliation: deCODE Genetics, Sturlugata 8, 101 Reykjavik, Iceland. patrick.sulem@decode.is
authors.forename: Patrick
authors.initials: P
authors.lastname: Sulem
authors.forename: Daniel F
authors.initials: DF
authors.lastname: Gudbjartsson
authors.forename: Frank
authors.initials: F
authors.lastname: Geller
authors.forename: Inga
authors.initials: I
authors.lastname: Prokopenko
authors.forename: Bjarke
authors.initials: B
authors.lastname: Feenstra
authors.forename: Katja K H
authors.initials: KK
authors.lastname: Aben
authors.forename: Barbara
authors.initials: B
authors.lastname: Franke
authors.forename: Martin
authors.initials: M
authors.lastname: den Heijer
authors.forename: Peter
authors.initials: P
authors.lastname: Kovacs
authors.forename: Michael
authors.initials: M
authors.lastname: Stumvoll
authors.forename: Reedik
authors.initials: R
authors.lastname: Mägi
authors.forename: Lisa R
authors.initials: LR
authors.lastname: Yanek
authors.forename: Lewis C
authors.initials: LC
authors.lastname: Becker
authors.forename: Heather A
authors.initials: HA
authors.lastname: Boyd
authors.forename: Simon N
authors.initials: SN
authors.lastname: Stacey
authors.forename: G Bragi
authors.initials: GB
authors.lastname: Walters
authors.forename: Adalbjorg
authors.initials: A
authors.lastname: Jonasdottir
authors.forename: Gudmar
authors.initials: G
authors.lastname: Thorleifsson
authors.forename: Hilma
authors.initials: H
authors.lastname: Holm
authors.forename: Sigurjon A
authors.initials: SA
authors.lastname: Gudjonsson
authors.forename: Thorunn
authors.initials: T
authors.lastname: Rafnar
authors.forename: Gyda
authors.initials: G
authors.lastname: Björnsdottir
authors.forename: Diane M
authors.initials: DM
authors.lastname: Becker
authors.forename: Mads
authors.initials: M
authors.lastname: Melbye
authors.forename: Augustine
authors.initials: A
authors.lastname: Kong
authors.forename: Anke
authors.initials: A
authors.lastname: Tönjes
authors.forename: Thorgeir
authors.initials: T
authors.lastname: Thorgeirsson
authors.forename: Unnur
authors.initials: U
authors.lastname: Thorsteinsdottir
authors.forename: Lambertus A
authors.initials: LA
authors.lastname: Kiemeney
authors.forename: Kari
authors.initials: K
authors.lastname: Stefansson
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002884:Chromosomes, Human, Pair 15; D003069:Coffee / Q000378:metabolism*; D019363:Cytochrome P-450 CYP1A1 / Q000235:genetics*; D019388:Cytochrome P-450 CYP1A2 / Q000235:genetics*; D004327:Drinking Behavior / Q000502:physiology*; D005260:Female; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic / Q000235:genetics; D018336:Receptors, Aryl Hydrocarbon / Q000235:genetics*; D012737:Sex Factors
chemical_list: D003069:Coffee; D018336:Receptors, Aryl Hydrocarbon; D019363:Cytochrome P-450 CYP1A1; D019388:Cytochrome P-450 CYP1A2