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 | |
| State | Published - Nov 2012 |
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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
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 journal › Article
}
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.
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 - coffee
KW - CYP1A1/CYP1A2
KW - NRCAM
KW - P450
KW - Parkinson's disease
UR - http://www.scopus.com/inward/record.url?scp=84861817713&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84861817713&partnerID=8YFLogxK
U2 - 10.1038/mp.2011.101
DO - 10.1038/mp.2011.101
M3 - Article
VL - 17
SP - 1116
EP - 1129
JO - Molecular Psychiatry
JF - Molecular Psychiatry
SN - 1359-4184
IS - 11
ER -