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 & 32 others 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

Research output: Contribution to journalArticle

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 languageEnglish (US)
Pages (from-to)1116-1129
Number of pages14
JournalMolecular Psychiatry
Volume17
Issue number11
DOIs
StatePublished - Nov 2012

Fingerprint

Cytochrome P-450 CYP1A2
Cytochrome P-450 CYP1A1
Genome-Wide Association Study
Coffee
Drinking
Caffeine
Single Nucleotide Polymorphism
Genes
Meta-Analysis
Addictive Behavior
Cell Line
5' Flanking Region
Polycyclic Aromatic Hydrocarbons
Linkage Disequilibrium
Proteasome Endopeptidase Complex
Ubiquitin
Down-Regulation
Genome
Blood Pressure
Gene Expression

Keywords

  • CAB39L
  • coffee
  • CYP1A1/CYP1A2
  • NRCAM
  • P450
  • Parkinson's disease

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., ... 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, 11.2012, p. 1116-1129.

Research output: Contribution to journalArticle

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 IM et al. Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Molecular Psychiatry. 2012 Nov;17(11):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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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

Y1 - 2012/11

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KW - CAB39L

KW - coffee

KW - CYP1A1/CYP1A2

KW - NRCAM

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KW - Parkinson's disease

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