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., kConFab Investigators, 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. ., Boomsma, D. I., Martin, N. G. and van Duijn, C. M. (2011) Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Molecular Psychiatry, 17 11: 1116-1129. doi:10.1038/mp.2011.101

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Author Amin, N.
Byrne, E.
Johnson, J.
Chenevix-Trench, G.
Walter, S.
Nolte, I. M.
kConFab Investigators
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. .
Boomsma, D. I.
Martin, N. G.
van Duijn, C. M.
Title Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM
Formatted title
Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM
Journal name Molecular Psychiatry   Check publisher's open access policy
ISSN 1359-4184
Publication date 2011-08
Sub-type Critical review of research, literature review, critical commentary
DOI 10.1038/mp.2011.101
Volume 17
Issue 11
Start page 1116
End page 1129
Total pages 14
Place of publication London, England,U.K.
Publisher Nature Publishing Group
Collection year 2012
Language eng
Formatted 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 (N=18 176) 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-values=1.6 × 10 -11 and 2.7 × 10 -11), which were also in strong linkage disequilibrium (r 2=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-value=3.9 × 10 -09) near NRCAM-a gene implicated in vulnerability to addiction, and at another independent hit rs6495122 (P-value=7.1 × 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-value=2.2 × 10 -05) and Parkinson's disease pathways (P-value=3.6 × 10 -05).
Keyword Coffee
Q-Index Code C1
Q-Index Status Confirmed Code
Institutional Status UQ
Additional Notes Article in Press, advance online publication 30 August 2011

Document type: Journal Article
Sub-type: Critical review of research, literature review, critical commentary
Collections: Queensland Brain Institute Publications
Official 2012 Collection
School of Medicine Publications
Institute for Molecular Bioscience - Publications
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Citation counts: TR Web of Science Citation Count  Cited 22 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 27 times in Scopus Article | Citations
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Created: Fri, 30 Sep 2011, 09:29:33 EST by Matthew Lamb on behalf of School of Medicine