Genes (Jul 2017)
Genetic Contribution to Alcohol Dependence: Investigation of a Heterogeneous German Sample of Individuals with Alcohol Dependence, Chronic Alcoholic Pancreatitis, and Alcohol-Related Cirrhosis
- Jens Treutlein,
- Josef Frank,
- Fabian Streit,
- Céline S. Reinbold,
- Dilafruz Juraeva,
- Franziska Degenhardt,
- Liz Rietschel,
- Stephanie H. Witt,
- Andreas J. Forstner,
- Monika Ridinger,
- Jana Strohmaier,
- Norbert Wodarz,
- Helene Dukal,
- Jerome C. Foo,
- Per Hoffmann,
- Stefan Herms,
- Stefanie Heilmann-Heimbach,
- Michael Soyka,
- Wolfgang Maier,
- Wolfgang Gaebel,
- Norbert Dahmen,
- Norbert Scherbaum,
- Bertram Müller-Myhsok,
- Susanne Lucae,
- Marcus Ising,
- Felix Stickel,
- Thomas Berg,
- Ulla Roggenbuck,
- Karl-Heinz Jöckel,
- Henrike Scholz,
- Ulrich S. Zimmermann,
- Stephan Buch,
- Wolfgang H. Sommer,
- Rainer Spanagel,
- Benedikt Brors,
- Sven Cichon,
- Karl Mann,
- Falk Kiefer,
- Jochen Hampe,
- Jonas Rosendahl,
- Markus M. Nöthen,
- Marcella Rietschel
Affiliations
- Jens Treutlein
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Josef Frank
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Fabian Streit
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Céline S. Reinbold
- Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland
- Dilafruz Juraeva
- Division of Applied Bioinformatics (G200), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Franziska Degenhardt
- Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany
- Liz Rietschel
- University Hospital of Child and Adolescent Psychiatry and Psychotherapy, University of Bern, 3000 Bern 60, Switzerland
- Stephanie H. Witt
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Andreas J. Forstner
- Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland
- Monika Ridinger
- Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany
- Jana Strohmaier
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Norbert Wodarz
- Department of Psychiatry and Psychotherapy, University of Regensburg, 93053 Regensburg, Germany
- Helene Dukal
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Jerome C. Foo
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Per Hoffmann
- Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland
- Stefan Herms
- Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland
- Stefanie Heilmann-Heimbach
- Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany
- Michael Soyka
- Private Hospital Meiringen, 3860 Meiringen, Switzerland
- Wolfgang Maier
- Department of Psychiatry, University of Bonn, 53105 Bonn, Germany
- Wolfgang Gaebel
- Department of Psychiatry and Psychotherapy, University of Düsseldorf, 40629 Düsseldorf, Germany
- Norbert Dahmen
- Department of Psychiatry, University of Mainz, 55131 Mainz, Germany
- Norbert Scherbaum
- LVR-Hospital Essen, Department of Psychiatry and Psychotherapy, Medical Faculty, University of Duisburg-Essen, 45147 Essen, Germany
- Bertram Müller-Myhsok
- Department of Statistical Genetics, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany
- Susanne Lucae
- Department of Psychiatric Pharmacogenetics, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany
- Marcus Ising
- Department of Molecular Psychology, Max-Planck-Institute of Psychiatry, 80804 Munich, Germany
- Felix Stickel
- Department of Gastroenterology and Hepatology, University Hospital of Zurich, 8091 Zurich, Switzerland
- Thomas Berg
- Section of Hepatology, University Hospital Leipzig, 04103 Leipzig, Germany
- Ulla Roggenbuck
- Institute for Medical Informatics, Biometry, and Epidemiology, University Hospital of Essen, 45122 Essen, Germany
- Karl-Heinz Jöckel
- Institute for Medical Informatics, Biometry, and Epidemiology, University Hospital of Essen, 45122 Essen, Germany
- Henrike Scholz
- Department of Animal Physiology, University of Cologne, 50674 Cologne, Germany
- Ulrich S. Zimmermann
- Department of Psychiatry and Psychotherapy, University Hospital Carl Gustav Carus, Dresden Technical University, 01307 Dresden, Germany
- Stephan Buch
- Medical Department 1, University Hospital Dresden, TU Dresden, 01307 Dresden, Germany
- Wolfgang H. Sommer
- Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Rainer Spanagel
- Institute of Psychopharmacology, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Benedikt Brors
- Division of Applied Bioinformatics (G200), German Cancer Research Center (DKFZ), 69120 Heidelberg, Germany
- Sven Cichon
- Human Genomics Research Group, Department of Biomedicine, University and University Hospital Basel, 4031 Basel, Switzerland
- Karl Mann
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Falk Kiefer
- Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- Jochen Hampe
- Medical Department 1, University Hospital Dresden, TU Dresden, 01307 Dresden, Germany
- Jonas Rosendahl
- Department of Internal Medicine I, Martin Luther University Halle, 06120 Halle (Saale), Germany
- Markus M. Nöthen
- Institute of Human Genetics, University of Bonn, 53127 Bonn, Germany
- Marcella Rietschel
- Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty Mannheim, Heidelberg University, 68159 Mannheim, Germany
- DOI
- https://doi.org/10.3390/genes8070183
- Journal volume & issue
-
Vol. 8,
no. 7
p. 183
Abstract
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 (puncorrected = 1.2 × 10−6; pcorrected = 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.
Keywords
- alcohol dependence
- chronic alcoholic pancreatitis
- alcoholic liver cirrhosis
- genome-wide association study
- alcohol dehydrogenase
- ADH1B
- ADH1C
