A National Research Priority Program of  
the

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Funding Period 2007 - 2010

P1

Analysis of novel nicotine dependence related candidate genes identified through a genome-wide association study

Prof. Dr. Norbert Dahmen (Coordinator & Principle Investigator)
University of Mainz
Dept. of Psychiatry
Untere Zahlbacherstr. 8

55131 Mainz
+49-6131-17-2920/3757
ndahmen(at)mail.psychiatrie.klinik.uni-mainz.de

 

Together with:

Prof. Dr. Heinz-Erich Wichmann (Principle Investigator)
GSF-National Research Center for Environment and Health (Helmholtz Institute)
Institute of Developmental genetics
Ingolstaedter Landstr. 1

85758 Neuherberg
+49-89-3187-4066
wichmann(at)gsf.de

Dr. Dan Rujescu (Principle Investigator)
Ludwig-Maximillians-University
Dept. of Psychiatry
Goethestr. 29

80336 Munich
+49-89-5160-5756
dan.rujescu(at)med.uni-muenchen.de

Prof. Dr. Andreas Gal (Principle Investigator)
University of Hamburg
Dept. of Human Genetics
Butenfeld 42

22529 Hamburg
+49-40-42803-3125
gal(at)uke.uni-hamburg.de

Georg Winterer, MD, PhD, (Principle Investigator)
Cologne Center for Genomics
University of Cologne
Weyertal 115b
50931 Cologne
+49-221-478-96847
Fax: +49-221-478-96866
georg.winterer(at)uni-koeln.de

Prof. Dr. Thomas Illig (Associate Investigator)
GSF-National Research Center for Environment and Health (Helmholtz Institute)
Institute of Epidemiology
Ingolstädter Landstr. 1

85758 Neuherberg
+49-89-3187-3623

Fax: +49-89-3187-4567

Illig(at)helmholtz-muenchen.de

Dr. Kirstin Mittelstrass (Associate Investigator)
GSF-National Research Center for Environment and Health (Helmholtz Institute)
Institute of Epidemiology
Ingolstaedter Landstr. 1,

85758 Neuherberg
+49-89-3187-3697

Fax: +49-89-3187-4567

kirstin.mittelstrass(at)helmholtz-muenchen.de

Prof. Dr. Karl-Heinz Ladwig (Associate Investigator)
GSF-National Research Center for Environment and Health (Helmholtz Institute)
Institute of Epidemiology
Ingolstaedter Landstr. 1

85758 Neuherberg
+49-89-3187-3623

Fax: +49-89-3187-4567
ladwig(at)gsf.de

 

Prof. Dr. Hermann Brenner (Associate Investigator)
German Cancer Research Center (Helmholtz Institute)
Dept. of Clinical Epidemiology and Aging Research
Bergheimer Str. 20

69115 Heidelberg
+49-6221-548156

Brenner(at)dkfz-heidelberg.de

Aim of the study is to identify genes which influence nicotine-related behaviour. Towards this end, we will employ the results of a state of the art (Affymetrix 500k chip) genome wide association study of 1200 subjects from the KORA-sample that is currently being carried out by the GSF together with partners from the German National Genome Research Network (NGFN) and that will be completed within 2006. The close interchange with NGFN resources in combination with sophistically characterized study samples ensures that internationally competitive and truly novel genes will be evaluated. A stepwise procedure will be pursued: 1) In the 1200 subjects positive association results will be ranked according to strength of statistical association, accordance with existing candidate gene studies and overlap with data from linkage and rodent QTL studies. 2) In another independent sample from the KORA-study (n=2000) with refined clinical characterization of smoking status and strength of nicotine dependence (a questionnaire-based quantitative measure for nicotine dependence, Fagerstrom test), we will seek to selectively replicate our initial findings (400 most promising SNPs from the initial scan). 3) As of the acknowledged clinical heterogeneity of the phenotype nicotine dependence, we will finally test the remaining best 50 single nucleotide polymorphisms (SNPs) for association in further samples which capture aspects of this heterogeneity a) the Munich/Berlin sample (n=2800) in which smoking status in conjunction with neuropsychological and electrophysiological endophenotyping of the quantitative traits attentional capacity and processing speed has been conducted (phenotypes known to be strongly related to nicotine dependence) b) the Mainz sample (n=300) which is extensively clinically characterized. The five most strongly associated genes during step 3 will be followed up by fine mapping of the involved genes including haplotype analyses. This step-wise procedure will also serve as prototype strategy for future analyses since it is expected that during the second funding period of the priority program, a large sample of carefully phenotyped subjects will be available derived from the prospectively conducted multicenter study which will also be part of the priority program. This will allow to investigate potential associations with other nicotine dependence-related phenotypes. Also, functional characterization of the discovered genes and genetic variations is planned for the second funding period.