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

School of Medicine

Research output: Contribution to journal › Review article

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 1 2012

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Keywords

CAB39L
CYP1A1/CYP1A2
NRCAM
P450
Parkinson's disease
coffee

ASJC Scopus subject areas

Molecular Biology
Psychiatry and Mental health
Cellular and Molecular Neuroscience

Cite this

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

Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. / 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.; Wray, N. R.; Montgomery, G. W.; Levy, D.; Psaty, B. M.; Gudnason, V.; Chakravarti, A.; Sulem, P.; Gudbjartsson, D. F.; Kiemeney, L. A.; Thorsteinsdottir, U.; Stefansson, K.; Van Rooij, F. J.A.; Aulchenko, Y. S.; Hottenga, J. J.; Rivadeneira, F. R.; Hofman, A.; Uitterlinden, A. G.; Hammond, C. J.; Shin, S. Y.; Ikram, A.; Witteman, J. C.M.; Janssens, A. C.J.W.; Snieder, H.; Tiemeier, H.; Wolfenbuttel, B. H.R.; Oostra, B. A.; Heath, A. C.; Wichmann, E.; Spector, T. D.; Grabe, H. J.; Boomsma, D. I.; Martin, N. G.; Van Duijn, C. M.

In: Molecular psychiatry, Vol. 17, No. 11, 01.11.2012, p. 1116-1129.

Research output: Contribution to journal › Review article

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

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. ; Wray, N. R. ; Montgomery, G. W. ; Levy, D. ; Psaty, B. M. ; Gudnason, V. ; Chakravarti, A. ; Sulem, P. ; Gudbjartsson, D. F. ; Kiemeney, L. A. ; Thorsteinsdottir, U. ; Stefansson, K. ; Van Rooij, F. J.A. ; Aulchenko, Y. S. ; Hottenga, J. J. ; Rivadeneira, F. R. ; Hofman, A. ; Uitterlinden, A. G. ; Hammond, C. J. ; Shin, S. Y. ; Ikram, A. ; Witteman, J. C.M. ; Janssens, A. C.J.W. ; Snieder, H. ; Tiemeier, H. ; Wolfenbuttel, B. H.R. ; Oostra, B. A. ; Heath, A. C. ; Wichmann, E. ; Spector, T. D. ; Grabe, H. J. ; Boomsma, D. I. ; Martin, N. G. ; Van Duijn, C. M. / Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. In: Molecular psychiatry. 2012 ; Vol. 17, No. 11. pp. 1116-1129.

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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.}",

year = "2012",

month = nov,

day = "1",

doi = "10.1038/mp.2011.101",

language = "English (US)",

volume = "17",

pages = "1116--1129",

journal = "Molecular Psychiatry",

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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.

PY - 2012/11/1

Y1 - 2012/11/1

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).

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10.1038/mp.2011.101