Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption by Sulem Patrick, Gudbjartsson Daniel F, Geller Frank, Prokopenko Inga, Feenstra Bjarke, Aben Katja K H, Franke Barbara, den Heijer Martin, Kovacs Peter, Stumvoll Michael, Mägi Reedik, Yanek Lisa R, Becker Lewis C, Boyd Heather A, Stacey Simon N, Walters G Bragi, Jonasdottir Adalbjorg, Thorleifsson Gudmar, Holm Hilma, Gudjonsson Sigurjon A, Rafnar Thorunn, Björnsdottir Gyda, Becker Diane M, Melbye Mads, Kong Augustine, Tönjes Anke, Thorgeirsson Thorgeir, Thorsteinsdottir Unnur, Kiemeney Lambertus A, Stefansson Kari in Human molecular genetics (2011).

[PMID: 21357676] PubMed


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.

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