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. 2017 Jul 17;8(7):183.
doi: 10.3390/genes8070183.

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  1 , Josef Frank  2 , Fabian Streit  3 , Céline S Reinbold  4   5 , Dilafruz Juraeva  6 , Franziska Degenhardt  7   8 , Liz Rietschel  9 , Stephanie H Witt  10 , Andreas J Forstner  11   12   13   14   15 , Monika Ridinger  16   17 , Jana Strohmaier  18 , Norbert Wodarz  19 , Helene Dukal  20 , Jerome C Foo  21 , Per Hoffmann  22   23   24   25 , Stefan Herms  26   27   28   29 , Stefanie Heilmann-Heimbach  30   31 , Michael Soyka  32   33 , Wolfgang Maier  34 , Wolfgang Gaebel  35 , Norbert Dahmen  36 , Norbert Scherbaum  37 , Bertram Müller-Myhsok  38 , Susanne Lucae  39 , Marcus Ising  40 , Felix Stickel  41   42 , Thomas Berg  43 , Ulla Roggenbuck  44 , Karl-Heinz Jöckel  45 , Henrike Scholz  46 , Ulrich S Zimmermann  47 , Stephan Buch  48 , Wolfgang H Sommer  49   50 , Rainer Spanagel  51 , Benedikt Brors  52 , Sven Cichon  53   54 , Karl Mann  55 , Falk Kiefer  56 , Jochen Hampe  57 , Jonas Rosendahl  58 , Markus M Nöthen  59   60 , Marcella Rietschel  61
Affiliations

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 et al. Genes (Basel). .

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: ADH1B; ADH1C; alcohol dehydrogenase; alcohol dependence; alcoholic liver cirrhosis; chronic alcoholic pancreatitis; genome-wide association study.

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Conflict of interest statement

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.

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