Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
21876539
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 (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)).
DATE PUBLISHED
2012 Nov
HISTORY
PUBSTATUS PUBSTATUSDATE
aheadofprint 2011/08/30
entrez 2011/08/31 06:00
pubmed 2011/08/31 06:00
medline 2013/04/24 06:00
AUTHORS
NAME COLLECTIVENAME LASTNAME FORENAME INITIALS AFFILIATION AFFILIATIONINFO
Amin N Amin N N Unit of Genetic Epidemiology, Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Byrne E Byrne E E
Johnson J Johnson J J
Chenevix-Trench G Chenevix-Trench G G
Walter S Walter S S
Nolte IM Nolte I M IM
kConFab Investigators
Vink JM Vink J M JM
Rawal R Rawal R R
Mangino M Mangino M M
Teumer A Teumer A A
Keers JC Keers J C JC
Verwoert G Verwoert G G
Baumeister S Baumeister S S
Biffar R Biffar R R
Petersmann A Petersmann A A
Dahmen N Dahmen N N
Doering A Doering A A
Isaacs A Isaacs A A
Broer L Broer L L
Wray NR Wray N R NR
Montgomery GW Montgomery G W GW
Levy D Levy D D
Psaty BM Psaty B M BM
Gudnason V Gudnason V V
Chakravarti A Chakravarti A A
Sulem P Sulem P P
Gudbjartsson DF Gudbjartsson D F DF
Kiemeney LA Kiemeney L A LA
Thorsteinsdottir U Thorsteinsdottir U U
Stefansson K Stefansson K K
van Rooij FJ van Rooij F J A FJ
Aulchenko YS Aulchenko Y S YS
Hottenga JJ Hottenga J J JJ
Rivadeneira FR Rivadeneira F R FR
Hofman A Hofman A A
Uitterlinden AG Uitterlinden A G AG
Hammond CJ Hammond C J CJ
Shin SY Shin S-Y SY
Ikram A Ikram A A
Witteman JC Witteman J C M JC
Janssens AC Janssens A C J W AC
Snieder H Snieder H H
Tiemeier H Tiemeier H H
Wolfenbuttel BH Wolfenbuttel B H R BH
Oostra BA Oostra B A BA
Heath AC Heath A C AC
Wichmann E Wichmann E E
Spector TD Spector T D TD
Grabe HJ Grabe H J HJ
Boomsma DI Boomsma D I DI
Martin NG Martin N G NG
van Duijn CM van Duijn C M CM
INVESTIGATORS
JOURNAL
VOLUME: 17
ISSUE: 11
TITLE: Molecular psychiatry
ISOABBREVIATION: Mol. Psychiatry
YEAR: 2012
MONTH: Nov
DAY:
MEDLINEDATE:
SEASON:
CITEDMEDIUM: Internet
ISSN: 1476-5578
ISSNTYPE: Electronic
MEDLINE JOURNAL
MEDLINETA: Mol Psychiatry
COUNTRY: England
ISSNLINKING: 1359-4184
NLMUNIQUEID: 9607835
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
Meta-Analysis
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
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GRANTS
GRANTID AGENCY COUNTRY
AA07535 NIAAA NIH HHS United States
AA10248 NIAAA NIH HHS United States
AA13320 NIAAA NIH HHS United States
AA13321 NIAAA NIH HHS United States
AA13326 NIAAA NIH HHS United States
AA14041 NIAAA NIH HHS United States
K05 AA017688 NIAAA NIH HHS United States
MH66206 NIMH NIH HHS United States
SRF/01/010 Department of Health United Kingdom
Biotechnology and Biological Sciences Research Council United Kingdom
Wellcome Trust United Kingdom
GENERAL NOTE
KEYWORDS
MESH HEADINGS
DESCRIPTORNAME QUALIFIERNAME
Antigens, Neoplasm genetics
Apoptosis Regulatory Proteins genetics
Caffeine pharmacology
Cell Adhesion Molecules genetics
Cell Line genetics
Coffee genetics
Cytochrome P-450 CYP1A1 genetics
Cytochrome P-450 CYP1A2 genetics
Drinking genetics
European Continental Ancestry Group genetics
Female genetics
Gene Expression drug effects
Gene Expression Profiling methods
Genetic Predisposition to Disease genetics
Genome-Wide Association Study methods
Humans methods
Male methods
Parkinson Disease genetics
Polymorphism, Single Nucleotide genetics
Protein-Serine-Threonine Kinases genetics
SUPPLEMENTARY MESH
GENE SYMBOLS
CHEMICALS
REGISTRYNUMBER NAMEOFSUBSTANCE
0 Antigens, Neoplasm
0 Apoptosis Regulatory Proteins
0 CAB39L protein, human
0 Cell Adhesion Molecules
0 Coffee
0 NRCAM protein, human
3G6A5W338E Caffeine
EC 1.14.14.1 CYP1A1 protein, human
EC 1.14.14.1 CYP1A2 protein, human
EC 1.14.14.1 Cytochrome P-450 CYP1A1
EC 1.14.14.1 Cytochrome P-450 CYP1A2
EC 2.7.11.1 Protein-Serine-Threonine Kinases
EC 2.7.11.1 ULK3 protein, human
OTHER ID's
OTHERID SOURCE
PMC3482684 NLM