Endocannabinoid gene × gene interaction association to alcohol use disorder in two adolescent cohorts
Genetic markers of endocannabinoid system have been linked to a variety of addiction-related behaviours that extend beyond cannabis use. In the current study we investigate the relationship between eCB genetic markers and AUDs in European adolescents (14-18 years old), followed in the IMAGEN study (...
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
20 April 2021
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| In: |
Frontiers in psychiatry
Year: 2021, Jahrgang: 12, Pages: 1-11 |
| ISSN: | 1664-0640 |
| DOI: | 10.3389/fpsyt.2021.645746 |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.3389/fpsyt.2021.645746 Verlag, lizenzpflichtig, Volltext: https://www.frontiersin.org/articles/10.3389/fpsyt.2021.645746/full 
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| Verfasserangaben: | Laurent Elkrief, Sean Spinney, Daniel E. Vosberg, Tobias Banaschewski, Arun L. W. Bokde, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Zdenka Pausova, Tomáš Paus, Guillaume Huguet, Patricia Conrod and the IMAGEN Consortium |
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| 245 | 1 | 0 | |a Endocannabinoid gene × gene interaction association to alcohol use disorder in two adolescent cohorts |c Laurent Elkrief, Sean Spinney, Daniel E. Vosberg, Tobias Banaschewski, Arun L. W. Bokde, Erin Burke Quinlan, Sylvane Desrivières, Herta Flor, Hugh Garavan, Penny Gowland, Andreas Heinz, Rüdiger Brühl, Jean-Luc Martinot, Marie-Laure Paillère Martinot, Frauke Nees, Dimitri Papadopoulos Orfanos, Luise Poustka, Sarah Hohmann, Sabina Millenet, Juliane H. Fröhner, Michael N. Smolka, Henrik Walter, Robert Whelan, Gunter Schumann, Zdenka Pausova, Tomáš Paus, Guillaume Huguet, Patricia Conrod and the IMAGEN Consortium |
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| 520 | |a Genetic markers of endocannabinoid system have been linked to a variety of addiction-related behaviours that extend beyond cannabis use. In the current study we investigate the relationship between eCB genetic markers and AUDs in European adolescents (14-18 years old), followed in the IMAGEN study (n=2051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) (n=772). Case-Control status is represented by a score of more than 7 on the Alcohol Use Disorder Identification Test (AUDIT). First a set-based test method was used to examine if a relationship between the eCB system and AUDIT case/control status exists, at the gene level. Using only SNPs that are both independent and significantly associated to case-control status, we perform Fisher’s exact test to determine SNP level odds ratios in relation to case-control status and then perform logistic regressions as post-hoc analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP x SNP interaction of the 5 eCB genes with positive AUDIT screen. While no gene-sets were significantly associated to AUDIT scores after correction for multiple tests, in the case/control analysis, 7 SNPs were significantly associated with AUDIT scores of > 7 (p<0.05; OR<1). Two SNPs remain significant after correction by false discovery rate (FDR); rs9343525 in CNR1 (pcorrected=0.04273, OR=0.729) and rs507961 in MGLL (pcorrected=0.04273, OR=0.784). Logistic regression showed that both rs9353525 (CNR1) and rs507961 (MGLL) remained significantly associated with positive AUDIT screens (p<0.01; OR<1), after correction for multiple covariables and interaction of covariable x SNP. This result was not replicated in the SYS cohort. The GMDR model revealed a significant three-SNP interaction (p= 0.006) involving rs484061 (MGLL), rs4963307 (DAGLA) and rs7766029 (CNR1) predicted case-control status, after correcting for multiple covariables in the IMAGEN sample. A binomial logistic regression of the combination of these three SNPs by phenotype in the SYS cohort showed a result in the same direction as seen in the IMAGEN cohort (BETA=0.501, p=0.06). While preliminary, the present study suggests that the eCB system may play a role in the development of AUD in adolescents. | ||
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