Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption

Patrick Sulem; Daniel F. Gudbjartsson; Frank Geller; Inga Prokopenko; Bjarke Feenstra; Katja K.H. Aben; Barbara Franke; Martin den Heijer; Peter Kovacs; Michael Stumvoll; Reedik Mägi; Lisa R. Yanek; Lewis Becker; Heather A. Boyd; Simon N. Stacey; G. Bragi Walters; Adalbjorg Jonasdottir; Gudmar Thorleifsson; Hilma Holm; Sigurjon A. Gudjonsson; Thorunn Rafnar; Gyda Björnsdottir; Diane M Becker; Mads Melbye; Augustine Kong; Anke Tönjes; Thorgeir Thorgeirsson; Unnur Thorsteinsdottir; Lambertus A. Kiemeney; Kari Stefansson

doi:10.1093/hmg/ddr086

Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption

Patrick Sulem, Daniel F. Gudbjartsson, Frank Geller, Inga Prokopenko, Bjarke Feenstra, Katja K.H. Aben, Barbara Franke, Martin den Heijer, Peter Kovacs, Michael Stumvoll, Reedik Mägi, Lisa R. Yanek, Lewis Becker, Heather A. Boyd, Simon N. Stacey, G. Bragi Walters, Adalbjorg Jonasdottir, Gudmar Thorleifsson, Hilma Holm, Sigurjon A. GudjonssonThorunn Rafnar, Gyda Björnsdottir, Diane M Becker, Mads Melbye, Augustine Kong, Anke Tönjes, Thorgeir Thorgeirsson, Unnur Thorsteinsdottir, Lambertus A. Kiemeney, Kari Stefansson

School of Medicine

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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 nonsmokers.

Original language	English (US)
Article number	ddr086
Pages (from-to)	2071-2077
Number of pages	7
Journal	Human molecular genetics
Volume	20
Issue number	10
DOIs	https://doi.org/10.1093/hmg/ddr086
State	Published - May 2011

ASJC Scopus subject areas

Molecular Biology
Genetics
Genetics(clinical)

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Sulem, P., Gudbjartsson, D. F., Geller, F., Prokopenko, I., Feenstra, B., Aben, K. K. H., Franke, B., den Heijer, M., Kovacs, P., Stumvoll, M., Mägi, R., Yanek, L. R., Becker, L., Boyd, H. A., Stacey, S. N., Walters, G. B., Jonasdottir, A., Thorleifsson, G., Holm, H., ... Stefansson, K. (2011). Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption. Human molecular genetics, 20(10), 2071-2077. Article ddr086. https://doi.org/10.1093/hmg/ddr086

Sulem, P, Gudbjartsson, DF, Geller, F, Prokopenko, I, Feenstra, B, Aben, KKH, Franke, B, den Heijer, M, Kovacs, P, Stumvoll, M, Mägi, R, Yanek, LR, Becker, L, Boyd, HA, Stacey, SN, Walters, GB, Jonasdottir, A, Thorleifsson, G, Holm, H, Gudjonsson, SA, Rafnar, T, Björnsdottir, G, Becker, DM, Melbye, M, Kong, A, Tönjes, A, Thorgeirsson, T, Thorsteinsdottir, U, Kiemeney, LA & Stefansson, K 2011, 'Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption', Human molecular genetics, vol. 20, no. 10, ddr086, pp. 2071-2077. https://doi.org/10.1093/hmg/ddr086

@article{018937a7b07744ddad1cbdca59e58b35,

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 nonsmokers.",

author = "Patrick Sulem and Gudbjartsson, {Daniel F.} and Frank Geller and Inga Prokopenko and Bjarke Feenstra and Aben, {Katja K.H.} and Barbara Franke and {den Heijer}, Martin and Peter Kovacs and Michael Stumvoll and Reedik M{\"a}gi and Yanek, {Lisa R.} and Lewis Becker and Boyd, {Heather A.} and Stacey, {Simon N.} and Walters, {G. Bragi} and Adalbjorg Jonasdottir and Gudmar Thorleifsson and Hilma Holm and Gudjonsson, {Sigurjon A.} and Thorunn Rafnar and Gyda Bj{\"o}rnsdottir and Becker, {Diane M} and Mads Melbye and Augustine Kong and Anke T{\"o}njes and Thorgeir Thorgeirsson and Unnur Thorsteinsdottir and Kiemeney, {Lambertus A.} and Kari Stefansson",

note = "Funding Information: This work was supported in part by grants from the NIH (R01-DA017932) and the European Commission (LSHM-CT-2004 – 005166). Dr Knut Krohn, Microarray Core Facility of the Interdisciplinary Centre for Clinical Research, University of Leipzig, Germany; German Research Council KFO-152 (to M.S.); IZKF B27 (to M.S., P.K. and A.T.). The research of Inga Prokopenko and Reedik M{\"a}gi is funded in part through the European Community{\textquoteright}s Seventh Framework Programme (FP7/2007 – 2013), ENGAGE project, grant agreement HEALTH-F4-2007-201413.",

year = "2011",

month = may,

doi = "10.1093/hmg/ddr086",

language = "English (US)",

volume = "20",

pages = "2071--2077",

journal = "Human molecular genetics",

issn = "0964-6906",

publisher = "Oxford University Press",

number = "10",

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T1 - Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption

AU - Sulem, Patrick

AU - Gudbjartsson, Daniel F.

AU - Geller, Frank

AU - Prokopenko, Inga

AU - Feenstra, Bjarke

AU - Aben, Katja K.H.

AU - Franke, Barbara

AU - den Heijer, Martin

AU - Kovacs, Peter

AU - Stumvoll, Michael

AU - Mägi, Reedik

AU - Yanek, Lisa R.

AU - Becker, Lewis

AU - Boyd, Heather A.

AU - Stacey, Simon N.

AU - Walters, G. Bragi

AU - Jonasdottir, Adalbjorg

AU - Thorleifsson, Gudmar

AU - Holm, Hilma

AU - Gudjonsson, Sigurjon A.

AU - Rafnar, Thorunn

AU - Björnsdottir, Gyda

AU - Becker, Diane M

AU - Melbye, Mads

AU - Kong, Augustine

AU - Tönjes, Anke

AU - Thorgeirsson, Thorgeir

AU - Thorsteinsdottir, Unnur

AU - Kiemeney, Lambertus A.

AU - Stefansson, Kari

N1 - Funding Information: This work was supported in part by grants from the NIH (R01-DA017932) and the European Commission (LSHM-CT-2004 – 005166). Dr Knut Krohn, Microarray Core Facility of the Interdisciplinary Centre for Clinical Research, University of Leipzig, Germany; German Research Council KFO-152 (to M.S.); IZKF B27 (to M.S., P.K. and A.T.). The research of Inga Prokopenko and Reedik Mägi is funded in part through the European Community’s Seventh Framework Programme (FP7/2007 – 2013), ENGAGE project, grant agreement HEALTH-F4-2007-201413.

PY - 2011/5

Y1 - 2011/5

N2 - 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 nonsmokers.

AB - 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 nonsmokers.

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Sequence variants at CYP1A1-CYP1A2 and AHR associate with coffee consumption

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