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Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM.
Mol Psychiatry 2012; 17(11):1116-29MP

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)).

Authors+Show Affiliations

Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

21876539

Citation

Amin, N, et al. "Genome-wide Association Analysis of Coffee Drinking Suggests Association With CYP1A1/CYP1A2 and NRCAM." Molecular Psychiatry, vol. 17, no. 11, 2012, pp. 1116-29.
Amin N, Byrne E, Johnson J, et al. Genome-wide association analysis of coffee drinking suggests association with CYP1A1/CYP1A2 and NRCAM. Mol Psychiatry. 2012;17(11):1116-29.
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), pp. 1116-29. doi:10.1038/mp.2011.101.
Amin N, et al. Genome-wide Association Analysis of Coffee Drinking Suggests Association With CYP1A1/CYP1A2 and NRCAM. Mol Psychiatry. 2012;17(11):1116-29. PubMed PMID: 21876539.
* Article titles in AMA citation format should be in sentence-case
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 - ,, 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, Y1 - 2011/08/30/ PY - 2011/8/31/entrez PY - 2011/8/31/pubmed PY - 2013/4/24/medline SP - 1116 EP - 29 JF - Molecular psychiatry JO - Mol. Psychiatry VL - 17 IS - 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 (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)). SN - 1476-5578 UR - https://www.unboundmedicine.com/medline/citation/21876539/Genome_wide_association_analysis_of_coffee_drinking_suggests_association_with_CYP1A1/CYP1A2_and_NRCAM_ L2 - http://dx.doi.org/10.1038/mp.2011.101 DB - PRIME DP - Unbound Medicine ER -