Genome-wide association study of pathological gambling.
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.



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.



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.



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.
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany. Electronic address: Maren.Lang@zi-mannheim.de.
M
M
Lang
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany.
T
T
Leménager
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany.
F
F
Streit
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany.
M
M
Fauth-Bühler
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany.
J
J
Frank
Division of Applied Bioinformatics, German Cancer Research Center, Heidelberg, Germany.
D
D
Juraeva
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany.
S H
SH
Witt
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
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F
Degenhardt
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
A
A
Hofmann
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
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S
Heilmann-Heimbach
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany.
F
F
Kiefer
Division of Applied Bioinformatics, German Cancer Research Center, Heidelberg, Germany.
B
B
Brors
Department of Psychiatry and Psychotherapy, University Medicine Greifswald, Helios Hospital Stralsund, Stralsund, Germany; German Center for Neurodegenerative Diseases (DZNE), Rostock/Greifswald, Germany.
H-J
HJ
Grabe
Department of Social Medicine and Prevention, University Medicine Greifswald, Greifswald, Germany; Partner site Greifswald, (DZHK) German Centre for Cardiovascular Research, Greifswald, Germany.
U
U
John
Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany.
A
A
Bischof
Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany.
G
G
Bischof
Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany; Partner site Greifswald, (DZHK) German Centre for Cardiovascular Research, Greifswald, Germany.
U
U
Völker
Department of Functional Genomics, University Medicine Greifswald, Greifswald, Germany.
G
G
Homuth
Kraichtal-Kliniken, Kraichtal, Germany.
M
M
Beutel
Department of Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
P A
PA
Lind
Department of Quantitative Genetics, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
S E
SE
Medland
Department of Psychological Sciences, University of Missouri, Columbia, MO, USA.
W S
WS
Slutske
Department of Genetic Epidemiology, QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
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NG
Martin
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.
H
H
Völzke
Institute of Human Genetics, University of Bonn, Bonn, Germany; Department of Genomics, Life & Brain Center, University of Bonn, Bonn, Germany.
M M
MM
Nöthen
Department of Social Medicine and Prevention, University Medicine Greifswald, Greifswald, Germany; Partner site Greifswald, (DZHK) German Centre for Cardiovascular Research, Greifswald, Germany.
C
C
Meyer
Department of Psychiatry and Psychotherapy, University of Luebeck, Luebeck, Germany.
H-J
HJ
Rumpf
Centre for Interdisciplinary Addiction Research (CIAR), University of Hamburg, Hamburg, Germany; Paracelsus Medical University, Salzburg, Austria.
F M
FM
Wurst
Department of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany.
M
M
Rietschel
Department of Addictive Behavior and Addiction Medicine, Central Institute of Mental Health, Medical Faculty, Mannheim/Heidelberg University, Mannheim, Germany.
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KF
Mann
D000328:Adult; D000437:Alcoholism / Q000235:genetics; D016739:Behavior, Addictive / Q000235:genetics* / Q000523:psychology; D015897:Comorbidity; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005715:Gambling / Q000235:genetics* / Q000523:psychology; D055106:Genome-Wide Association Study; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D019966:Substance-Related Disorders / Q000235:genetics
Addiction; Association; Gambling; Genetics; Genome-wide