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Genome-wide association study of pathological gambling
- M. Lang, T. Leménager, F. Streit, M. Fauth-Bühler, J. Frank, D. Juraeva, S.H. Witt, F. Degenhardt, A. Hofmann, S. Heilmann-Heimbach, F. Kiefer, B. Brors, H.-J. Grabe, U. John, A. Bischof, G. Bischof, U. Völker, G. Homuth, M. Beutel, P.A. Lind, S.E. Medland, W.S. Slutske, N.G. Martin, H. Völzke, M.M. Nöthen, C. Meyer, H.-J. Rumpf, F.M. Wurst, M. Rietschel, K.F. Mann
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- Journal:
- European Psychiatry / Volume 36 / August 2016
- Published online by Cambridge University Press:
- 23 March 2020, pp. 38-46
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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.
MethodsFour 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.
ResultsNo 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.
ConclusionsThe 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.
An Integrative Approach for Studying the Etiology of Alcoholism and Other Addictions
- T. Jacob, K.J. Sher, K.K. Bucholz, W.T. True, E.J. Sirevaag, J. Rohrbaugh, E. Nelson, R.J. Neuman, R.D. Todd, W.S. Slutske, J.B. Whitfield, K.M. Kirk, N.G. Martin, P.A.F. Madden, A.C. Heath
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- Journal:
- Twin Research / Volume 4 / Issue 2 / 01 April 2001
- Published online by Cambridge University Press:
- 21 February 2012, pp. 103-118
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Studies of alcoholism etiology often focus on genetic or psy-chosocial approaches, but not both. Greater understanding of the etiology of alcohol, tobacco and other addictions will come from integration of these research traditions. A research approach is outlined to test three models for the etiology of addictions — behavioral undercontrol, pharmacologic vulnerability, negative affect regulation — addressing key questions including (i) mediators of genetic effects, (ii) genotype-environment correlation effects, (iii) genotype x environment interaction effects, (iv) the developmental unfolding of genetic and environmental effects, (v) subtyping including identification of distinct trajectories of substance involvement, (vi) identification of individual genes that contribute to risk, and (vii) the consequences of excessive use. By using coordinated research designs, including prospective assessment of adolescent twins and their siblings and parents; of adult substance dependent and control twins and their MZ and DZ cotwins, the spouses of these pairs, and their adolescent offspring; and of regular families; by selecting for gene-mapping approaches sibships screened for extreme concordance or discordance on quantitative indices of substance use; and by using experimental (drug challenge) as well as survey approaches, a number of key questions concerning addiction etiology can be addressed. We discuss complementary strengths and weaknesses of different sampling strategies, as well as methods to implement such an integrated approach illustrated for the study of alcoholism etiology. A coordinated program of twin and family studies will allow a comprehensive dissection of the interplay of genetic and environmental risk-factors in the etiology of alcoholism and other addictions.