Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis.

Autor: Treutlein J; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. jens.treutlein@zi-mannheim.de., Frank J; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. josef.frank@zi-mannheim.de., Streit F; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. fabian.streit@zi-mannheim.de., Reinbold CS; Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland. celine.reinbold@unibas.ch.; Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, Switzerland. celine.reinbold@unibas.ch., Juraeva D; Division of Applied Bioinformatics (G200), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. juraeva@yahoo.com., Degenhardt F; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. franziska.degenhardt@uni-bonn.de.; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany. franziska.degenhardt@uni-bonn.de., Rietschel L; University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, 3000 Bern 60, Switzerland. liz.rietschel@kjp.unibe.ch., Witt SH; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. stephanie.witt@zi-mannheim.de., Forstner AJ; Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland. forstner@uni-bonn.de.; Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, Switzerland. forstner@uni-bonn.de.; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. forstner@uni-bonn.de.; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany. forstner@uni-bonn.de.; Department of Psychiatry (U.P.K.), University of Basel, CH-4002 Basel, Switzerland. forstner@uni-bonn.de., Ridinger M; Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany. monika.ridinger@gmx.ch.; Psychiatric Health Care Aargau, 5210 Windisch, Switzerland. monika.ridinger@gmx.ch., Strohmaier J; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. jana.strohmaier@zi-mannheim.de., Wodarz N; Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany. norbert.wodarz@medbo.de., Dukal H; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. helene.dukal@zi-mannheim.de., Foo JC; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. jerome.foo@zi-mannheim.de., Hoffmann P; Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland. per.hoffmann@unibas.ch.; Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, Switzerland. per.hoffmann@unibas.ch.; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. per.hoffmann@unibas.ch.; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany. per.hoffmann@unibas.ch., Herms S; Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland. stefan.herms@unibas.ch.; Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, Switzerland. stefan.herms@unibas.ch.; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. stefan.herms@unibas.ch.; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany. stefan.herms@unibas.ch., Heilmann-Heimbach S; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. sheilman@uni-bonn.de.; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany. sheilman@uni-bonn.de., Soyka M; Private Hospital Meiringen, 3860 Meiringen, Switzerland. Michael.Soyka@privatklinik-meiringen.ch.; Psychiatric Hospital, Ludwig Maximilians University, 80336 Munich, Germany. Michael.Soyka@privatklinik-meiringen.ch., Maier W; Department of Psychiatry, University of Bonn, 53105 Bonn, Germany. Wolfgang.Maier@ukb.uni-bonn.de., Gaebel W; Department of Psychiatry and Psychotherapy, University of Düsseldorf, 40629 Düsseldorf, Germany. wolfgang.gaebel@uni-duesseldorf.de., Dahmen N; Department of Psychiatry, University of Mainz, 55131 Mainz, Germany. n.dahmen@oehk.de., Scherbaum N; LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany. norbert.scherbaum@uni-due.de., Müller-Myhsok B; Department of Statistical Genetics, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany. bmm@mpipsykl.mpg.de., Lucae S; Department of Psychiatric Pharmacogenetics, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany. lucae@psych.mpg.de., Ising M; Department of Molecular Psychology, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany. ising@psych.mpg.de., Stickel F; Department of Gastroenterology and Hepatology, University Hospital of Zurich, 8091 Zurich, Switzerland. Felix.stickel@uzh.ch.; Hirslanden Private Hospital, 8032 Hirslanden Zürich, Switzerland. Felix.stickel@uzh.ch., Berg T; Section of Hepatology, University Hospital Leipzig, 04103 Leipzig, Germany. Thomas.Berg@medizin.uni-leipzig.de., Roggenbuck U; Institute for Medical Informatics, Biometry, and Epidemiology, University Hospital of Essen, 45122 Essen, Germany. Ulla.Roggenbuck@uk-essen.de., Jöckel KH; Institute for Medical Informatics, Biometry, and Epidemiology, University Hospital of Essen, 45122 Essen, Germany. k-h.joeckel@uk-essen.de., Scholz H; Department of Animal Physiology, University of Cologne, 50674 Cologne, Germany. henrike.scholz@uni-koeln.de., Zimmermann US; Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Dresden Technical University, 01307 Dresden, Germany. UlrichS.Zimmermann@uniklinikum-dresden.de., Buch S; Medical Department 1, University Hospital Dresden, TU Dresden, 01307 Dresden, Germany. Stephan.Buch@uniklinikum-dresden.de., Sommer WH; Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. wolfgang.sommer@zi-mannheim.de.; Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. wolfgang.sommer@zi-mannheim.de., Spanagel R; Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. rainer.spanagel@zi-mannheim.de., Brors B; Division of Applied Bioinformatics (G200), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany. b.brors@dkfz.de., Cichon S; Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland. sven.cichon@unibas.ch.; Institute of Medical Genetics and Pathology, University Hospital Basel, 4031 Basel, Switzerland. sven.cichon@unibas.ch., Mann K; Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. karl.mann@zi-mannheim.de., Kiefer F; Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. falk.kiefer@zi-mannheim.de., Hampe J; Medical Department 1, University Hospital Dresden, TU Dresden, 01307 Dresden, Germany. Jochen.Hampe@uniklinikum-dresden.de., Rosendahl J; Department of Internal Medicine I, Martin Luther University Halle, 06120 Halle (Saale), Germany. Jonas.Rosendahl@medizin.uni-leipzig.de., Nöthen MM; Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany. markus.noethen@uni-bonn.de.; Department of Genomics, Life & Brain Center, University of Bonn, 53127 Bonn, Germany. markus.noethen@uni-bonn.de., Rietschel M; Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany. marcella.rietschel@zi-mannheim.de.
Jazyk: angličtina
Zdroj: Genes [Genes (Basel)] 2017 Jul 17; Vol. 8 (7). Date of Electronic Publication: 2017 Jul 17.
DOI: 10.3390/genes8070183
Abstrakt: The present study investigated the genetic contribution to alcohol dependence (AD) using genome-wide association data from three German samples. These comprised patients with: (i) AD; (ii) chronic alcoholic pancreatitis (ACP); and (iii) alcohol-related liver cirrhosis (ALC). Single marker, gene-based, and pathway analyses were conducted. A significant association was detected for the ADH1B locus in a gene-based approach ( p uncorrected = 1.2 × 10 -6 ; p corrected = 0.020). This was driven by the AD subsample. No association with ADH1B was found in the combined ACP + ALC sample. On first inspection, this seems surprising, since ADH1B is a robustly replicated risk gene for AD and may therefore be expected to be associated also with subgroups of AD patients. The negative finding in the ACP + ALC sample, however, may reflect genetic stratification as well as random fluctuation of allele frequencies in the cases and controls, demonstrating the importance of large samples in which the phenotype is well assessed.
Competing Interests: Norbert Scherbaum has received honoraria from Sanofi-Aventis, Reckitt-Benckiser/Indivior, Lundbeck, and Janssen-Cilag for advisory board participation, lectures, and the preparation of manuscripts and educational materials. In the past three years, he has participated in clinical trials financed by the pharmaceutical industry (Reckitt & Benckiser/Indivior). These funding sources had no role in the design of the study; in the collection, analysis, or interpretation of data; in the writing of the manuscript, or and the decision to publish the results.
Databáze: MEDLINE
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