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Genome-wide association study of pathological gambling

Published online by Cambridge University Press:  23 March 2020

M. Lang ,
T. Leménager ,
F. Streit ,
M. Fauth-Bühler ,
J. Frank ,
D. Juraeva ,
S.H. Witt ,
F. Degenhardt ,
A. Hofmann  and
S. Heilmann-Heimbach
...Show all authors
M. Lang*
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany Contributed equally.
T. Leménager
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany Contributed equally.
F. Streit
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany
M. Fauth-Bühler
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany
J. Frank
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany
D. Juraeva
Affiliation:
Division of Applied Bioinformatics, German Cancer Research Center, Heidelberg, Germany
S.H. Witt
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany
F. Degenhardt
Affiliation:
Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
A. Hofmann
Affiliation:
Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
S. Heilmann-Heimbach
Affiliation:
Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
F. Kiefer
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany
B. Brors
Affiliation:
Division of Applied Bioinformatics, German Cancer Research Center, Heidelberg, Germany
H.-J. Grabe
Affiliation:
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Helios Hospital Stralsund, Stralsund, Germany German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany
U. John
Affiliation:
Department of Social Medicine and Prevention, University Medicine Greifswald, Greifswald, Germany Partner site Greifswald, (DZHK) German Centre for Cardiovascular Research, Greifswald, Germany
A. Bischof
Affiliation:
Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany
G. Bischof
Affiliation:
Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany
U. Völker
Affiliation:
Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany Partner site Greifswald, (DZHK) German Centre for Cardiovascular Research, Greifswald, Germany
G. Homuth
Affiliation:
Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany
M. Beutel
Affiliation:
Kraichtal-Kliniken, Kraichtal, Germany
P.A. Lind
Affiliation:
Department of Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
S.E. Medland
Affiliation:
Department of Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
W.S. Slutske
Affiliation:
Department of Psychological Sciences, University of Missouri, Columbia, MO, USA
N.G. Martin
Affiliation:
Department of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia
H. Völzke
Affiliation:
Institute for Community Medicine, University of Greifswald, Center for Dental, Oral and Maxillofacial Medicine, University of Greifswald, Institute of Social Medicine and Prevention, University of Greifswald, Greifswald, Germany Partner site Greifswald, (DZHK) German Centre for Cardiovascular Research, Greifswald, Germany
M.M. Nöthen
Affiliation:
Institute of Human Genetics, University of Bonn, Bonn, Germany Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany
C. Meyer
Affiliation:
Department of Social Medicine and Prevention, University Medicine Greifswald, Greifswald, Germany Partner site Greifswald, (DZHK) German Centre for Cardiovascular Research, Greifswald, Germany
H.-J. Rumpf
Affiliation:
Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany
F.M. Wurst
Affiliation:
Centre for Interdisciplinary Addiction Research (CIAR), University of Hamburg, Hamburg, Germany Paracelsus Medical University, Salzburg, Austria
M. Rietschel
Affiliation:
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany Contributed equally.
K.F. Mann
Affiliation:
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany Contributed equally.
*
⁎Corresponding author. Department of Genetic Epidemiology in Psychiatry Central Institute of Mental Health, J5, 68159 Mannheim, Germany. Tel.: +49 621 1703 6093; fax: +49 621 1703 6065. [email protected]
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Abstract

Background

Pathological gambling is a behavioural addiction with negative economic, social, and psychological consequences. Identification of contributing genes and pathways may improve understanding of aetiology and facilitate therapy and prevention. Here, we report the first genome-wide association study of pathological gambling. Our aims were to identify pathways involved in pathological gambling, and examine whether there is a genetic overlap between pathological gambling and alcohol dependence.

Methods

Four hundred and forty-five individuals with a diagnosis of pathological gambling according to the Diagnostic and Statistical Manual of Mental Disorders were recruited in Germany, and 986 controls were drawn from a German general population sample. A genome-wide association study of pathological gambling comprising single marker, gene-based, and pathway analyses, was performed. Polygenic risk scores were generated using data from a German genome-wide association study of alcohol dependence.

Results

No genome-wide significant association with pathological gambling was found for single markers or genes. Pathways for Huntington's disease (P-value = 6.63 × 10−3); 5′-adenosine monophosphate-activated protein kinase signalling (P-value = 9.57 × 10−3); and apoptosis (P-value = 1.75 × 10−2) were significant. Polygenic risk score analysis of the alcohol dependence dataset yielded a one-sided nominal significant P-value in subjects with pathological gambling, irrespective of comorbid alcohol dependence status.

Conclusions

The present results accord with previous quantitative formal genetic studies which showed genetic overlap between non-substance- and substance-related addictions. Furthermore, pathway analysis suggests shared pathology between Huntington's disease and pathological gambling. This finding is consistent with previous imaging studies.

Keywords

GamblingGenome-wideAssociationAddictionGenetics
Type
Original article
Information
European Psychiatry , Volume 36 , August 2016 , pp. 38 - 46
Copyright
Copyright © European Psychiatric Association 2016

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