Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM

N. Amin; E. Byrne; J. Johnson; G. Chenevix-Trench; S. Walter; I. M. Nolte; J. M. Vink; R. Rawal; M. Mangino; A. Teumer; J. C. Keers; G. Verwoert; S. Baumeister; R. Biffar; A. Petersmann; N. Dahmen; A. Doering; A. Isaacs; L. Broer; N. R. Wray; G. W. Montgomery; D. Levy; B. M. Psaty; V. Gudnason; A. Chakravarti; P. Sulem; D. F. Gudbjartsson; L. A. Kiemeney; U. Thorsteinsdottir; K. Stefansson; F. J.A. Van Rooij; Y. S. Aulchenko; J. J. Hottenga; F. R. Rivadeneira; A. Hofman; A. G. Uitterlinden; C. J. Hammond; S. Y. Shin; A. Ikram; J. C.M. Witteman; A. C.J.W. Janssens; H. Snieder; H. Tiemeier; B. H.R. Wolfenbuttel; B. A. Oostra; A. C. Heath; E. Wichmann; T. D. Spector; H. J. Grabe; D. I. Boomsma; N. G. Martin; C. M. Van Duijn

doi:10.1038/mp.2011.101

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM

N. Amin, E. Byrne, J. Johnson, G. Chenevix-Trench, S. Walter, I. M. Nolte, J. M. Vink, R. Rawal, M. Mangino, A. Teumer, J. C. Keers, G. Verwoert, S. Baumeister, R. Biffar, A. Petersmann, N. Dahmen, A. Doering, A. Isaacs, L. Broer, N. R. WrayG. W. Montgomery, D. Levy, B. M. Psaty, V. Gudnason, A. Chakravarti, P. Sulem, D. F. Gudbjartsson, L. A. Kiemeney, U. Thorsteinsdottir, K. Stefansson, F. J.A. Van Rooij, Y. S. Aulchenko, J. J. Hottenga, F. R. Rivadeneira, A. Hofman, A. G. Uitterlinden, C. J. Hammond, S. Y. Shin, A. Ikram, J. C.M. Witteman, A. C.J.W. Janssens, H. Snieder, H. Tiemeier, B. H.R. Wolfenbuttel, B. A. Oostra, A. C. Heath, E. Wichmann, T. D. Spector, H. J. Grabe, D. I. Boomsma, N. G. Martin, C. M. Van Duijn

Research output: Contribution to journal › Review article › peer-review

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Abstract

Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values1.6 × 10^-11 and 2.7 × 10^-11), which were also in strong linkage disequilibrium (r² 0.7) with each other, lie in the 23-kb long commonly shared 5′ flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value3.9 × 10 09) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value7.1 × 10 ^-09)-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value2.2 × 10 ^-05) and Parkinson's disease pathways (P-value3.6 × 10 ^-05).

Original language	English (US)
Pages (from-to)	1116-1129
Number of pages	14
Journal	Molecular psychiatry
Volume	17
Issue number	11
DOIs	https://doi.org/10.1038/mp.2011.101
State	Published - Nov 2012
Externally published	Yes

Keywords

CAB39L
CYP1A1/CYP1A2
NRCAM
P450
Parkinson's disease
coffee

ASJC Scopus subject areas

Molecular Biology
Cellular and Molecular Neuroscience
Psychiatry and Mental health

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10.1038/mp.2011.101

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Amin, N., Byrne, E., Johnson, J., Chenevix-Trench, G., Walter, S., Nolte, I. M., Vink, J. M., Rawal, R., Mangino, M., Teumer, A., Keers, J. C., Verwoert, G., Baumeister, S., Biffar, R., Petersmann, A., Dahmen, N., Doering, A., Isaacs, A., Broer, L., ... Van Duijn, C. M. (2012). Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Molecular psychiatry, 17(11), 1116-1129. https://doi.org/10.1038/mp.2011.101

Amin, N, Byrne, E, Johnson, J, Chenevix-Trench, G, Walter, S, Nolte, IM, Vink, JM, Rawal, R, Mangino, M, Teumer, A, Keers, JC, Verwoert, G, Baumeister, S, Biffar, R, Petersmann, A, Dahmen, N, Doering, A, Isaacs, A, Broer, L, Wray, NR, Montgomery, GW, Levy, D, Psaty, BM, Gudnason, V, Chakravarti, A, Sulem, P, Gudbjartsson, DF, Kiemeney, LA, Thorsteinsdottir, U, Stefansson, K, Van Rooij, FJA, Aulchenko, YS, Hottenga, JJ, Rivadeneira, FR, Hofman, A, Uitterlinden, AG, Hammond, CJ, Shin, SY, Ikram, A, Witteman, JCM, Janssens, ACJW, Snieder, H, Tiemeier, H, Wolfenbuttel, BHR, Oostra, BA, Heath, AC, Wichmann, E, Spector, TD, Grabe, HJ, Boomsma, DI, Martin, NG & Van Duijn, CM 2012, 'Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM', Molecular psychiatry, vol. 17, no. 11, pp. 1116-1129. https://doi.org/10.1038/mp.2011.101

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title = "Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM",

abstract = "Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values1.6 × 10-11 and 2.7 × 10-11), which were also in strong linkage disequilibrium (r2 0.7) with each other, lie in the 23-kb long commonly shared 5′ flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value3.9 × 10 09) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value7.1 × 10 -09)-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value2.2 × 10 -05) and Parkinson's disease pathways (P-value3.6 × 10 -05).",

keywords = "CAB39L, CYP1A1/CYP1A2, NRCAM, P450, Parkinson's disease, coffee",

author = "N. Amin and E. Byrne and J. Johnson and G. Chenevix-Trench and S. Walter and Nolte, {I. M.} and Vink, {J. M.} and R. Rawal and M. Mangino and A. Teumer and Keers, {J. C.} and G. Verwoert and S. Baumeister and R. Biffar and A. Petersmann and N. Dahmen and A. Doering and A. Isaacs and L. Broer and Wray, {N. R.} and Montgomery, {G. W.} and D. Levy and Psaty, {B. M.} and V. Gudnason and A. Chakravarti and P. Sulem and Gudbjartsson, {D. F.} and Kiemeney, {L. A.} and U. Thorsteinsdottir and K. Stefansson and {Van Rooij}, {F. J.A.} and Aulchenko, {Y. S.} and Hottenga, {J. J.} and Rivadeneira, {F. R.} and A. Hofman and Uitterlinden, {A. G.} and Hammond, {C. J.} and Shin, {S. Y.} and A. Ikram and Witteman, {J. C.M.} and Janssens, {A. C.J.W.} and H. Snieder and H. Tiemeier and Wolfenbuttel, {B. H.R.} and Oostra, {B. A.} and Heath, {A. C.} and E. Wichmann and Spector, {T. D.} and Grabe, {H. J.} and Boomsma, {D. I.} and Martin, {N. G.} and {Van Duijn}, {C. M.}",

note = "Funding Information: ERF: The genotyping for the ERF study was supported by EUROSPAN (European Special Populations Research Network) and the European Commission FP6 STRP grant (018947; LSHG-CT-2006-01947). The ERF study was further supported by grants from the Netherlands Organization for Scientific Research, Erasmus MC, the Centre for Medical Systems Biology (CMSB) and the Netherlands Brain Foundation (HersenStichting Nederland). We are grateful to all patients and their relatives, general practitioners and neurologists for their contributions and to P Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. We acknowledge Internationale Stichting Alzheimer Onderzoek (ISAO) and Hersenstichting Netherlands. KORA: The KORA Augsburg studies were financed by the Helmholtz Zentrum M{\"u}nchen, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF). Part of this work was financed by the German National Genome Research Network (NGFN). Our research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. Netherlands Twin Register(NTR): We acknowledge support from: Genetic basis of anxiety and depression (904-61-090); Twin-family database for behavior",

year = "2012",

month = nov,

doi = "10.1038/mp.2011.101",

language = "English (US)",

volume = "17",

pages = "1116--1129",

journal = "Molecular psychiatry",

issn = "1359-4184",

publisher = "Nature Publishing Group",

number = "11",

}

TY - JOUR

T1 - Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM

AU - Amin, N.

AU - Byrne, E.

AU - Johnson, J.

AU - Chenevix-Trench, G.

AU - Walter, S.

AU - Nolte, I. M.

AU - Vink, J. M.

AU - Rawal, R.

AU - Mangino, M.

AU - Teumer, A.

AU - Keers, J. C.

AU - Verwoert, G.

AU - Baumeister, S.

AU - Biffar, R.

AU - Petersmann, A.

AU - Dahmen, N.

AU - Doering, A.

AU - Isaacs, A.

AU - Broer, L.

AU - Wray, N. R.

AU - Montgomery, G. W.

AU - Levy, D.

AU - Psaty, B. M.

AU - Gudnason, V.

AU - Chakravarti, A.

AU - Sulem, P.

AU - Gudbjartsson, D. F.

AU - Kiemeney, L. A.

AU - Thorsteinsdottir, U.

AU - Stefansson, K.

AU - Van Rooij, F. J.A.

AU - Aulchenko, Y. S.

AU - Hottenga, J. J.

AU - Rivadeneira, F. R.

AU - Hofman, A.

AU - Uitterlinden, A. G.

AU - Hammond, C. J.

AU - Shin, S. Y.

AU - Ikram, A.

AU - Witteman, J. C.M.

AU - Janssens, A. C.J.W.

AU - Snieder, H.

AU - Tiemeier, H.

AU - Wolfenbuttel, B. H.R.

AU - Oostra, B. A.

AU - Heath, A. C.

AU - Wichmann, E.

AU - Spector, T. D.

AU - Grabe, H. J.

AU - Boomsma, D. I.

AU - Martin, N. G.

AU - Van Duijn, C. M.

N1 - Funding Information: ERF: The genotyping for the ERF study was supported by EUROSPAN (European Special Populations Research Network) and the European Commission FP6 STRP grant (018947; LSHG-CT-2006-01947). The ERF study was further supported by grants from the Netherlands Organization for Scientific Research, Erasmus MC, the Centre for Medical Systems Biology (CMSB) and the Netherlands Brain Foundation (HersenStichting Nederland). We are grateful to all patients and their relatives, general practitioners and neurologists for their contributions and to P Veraart for her help in genealogy, Jeannette Vergeer for the supervision of the laboratory work and P Snijders for his help in data collection. We acknowledge Internationale Stichting Alzheimer Onderzoek (ISAO) and Hersenstichting Netherlands. KORA: The KORA Augsburg studies were financed by the Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany, and supported by grants from the German Federal Ministry of Education and Research (BMBF). Part of this work was financed by the German National Genome Research Network (NGFN). Our research was supported within the Munich Center of Health Sciences (MC Health) as part of LMUinnovativ. Netherlands Twin Register(NTR): We acknowledge support from: Genetic basis of anxiety and depression (904-61-090); Twin-family database for behavior

PY - 2012/11

Y1 - 2012/11

N2 - Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values1.6 × 10-11 and 2.7 × 10-11), which were also in strong linkage disequilibrium (r2 0.7) with each other, lie in the 23-kb long commonly shared 5′ flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value3.9 × 10 09) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value7.1 × 10 -09)-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value2.2 × 10 -05) and Parkinson's disease pathways (P-value3.6 × 10 -05).

AB - Coffee consumption is a model for addictive behavior. We performed a meta-analysis of genome-wide association studies (GWASs) on coffee intake from 8 Caucasian cohorts (N18 176) and sought replication of our top findings in a further 7929 individuals. We also performed a gene expression analysis treating different cell lines with caffeine. Genome-wide significant association was observed for two single-nucleotide polymorphisms (SNPs) in the 15q24 region. The two SNPs rs2470893 and rs2472297 (P-values1.6 × 10-11 and 2.7 × 10-11), which were also in strong linkage disequilibrium (r2 0.7) with each other, lie in the 23-kb long commonly shared 5′ flanking region between CYP1A1 and CYP1A2 genes. CYP1A1 was found to be downregulated in lymphoblastoid cell lines treated with caffeine. CYP1A1 is known to metabolize polycyclic aromatic hydrocarbons, which are important constituents of coffee, whereas CYP1A2 is involved in the primary metabolism of caffeine. Significant evidence of association was also detected at rs382140 (P-value3.9 × 10 09) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value7.1 × 10 -09)-an SNP associated with blood pressure-in the 15q24 region near the gene ULK3, in the meta-analysis of discovery and replication cohorts. Our results from GWASs and expression analysis also strongly implicate CAB39L in coffee drinking. Pathway analysis of differentially expressed genes revealed significantly enriched ubiquitin proteasome (P-value2.2 × 10 -05) and Parkinson's disease pathways (P-value3.6 × 10 -05).

KW - CAB39L

KW - CYP1A1/CYP1A2

KW - NRCAM

KW - P450

KW - Parkinson's disease

KW - coffee

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U2 - 10.1038/mp.2011.101

DO - 10.1038/mp.2011.101

M3 - Review article

C2 - 21876539

AN - SCOPUS:84861817713

SN - 1359-4184

VL - 17

SP - 1116

EP - 1129

JO - Molecular psychiatry

JF - Molecular psychiatry

IS - 11

ER -

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM

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