The Experts below are selected from a list of 656259 Experts worldwide ranked by ideXlab platform

Gowland Penny - One of the best experts on this subject based on the ideXlab platform.

  • Endocannabinoid gene × gene interaction association to alcohol use disorder in two adolescent cohorts.
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Bokde, Arun L W, Quinlan, Erin Burke, Desrivières Sylvane, Flor Herta, Garavan Hugh, Gowland Penny
    Abstract:

    Genetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study ( = 2,051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) ( = 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 analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP×SNP interaction of the five 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 ( < 0.05; OR

  • Endocannabinoid Gene × Gene Interaction Association to Alcohol Use Disorder in Two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Vosberg Daniel, Bokde Arun, Quinlan Erin, Gowland Penny
    Abstract:

    International audienceGenetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study (n = 2,051) 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×SNP interaction of the five 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

  • Endocannabinoid Gene x Gene Interaction Association to Alcohol Use Disorder in two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Bokde Arun, Quinlan, Erin B, Gowland Penny
    Abstract:

    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 [less than] 0.05; OR [less than] 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 [less than] 0.01; OR[less than] 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

Elkrief Laurent - One of the best experts on this subject based on the ideXlab platform.

  • Endocannabinoid gene × gene interaction association to alcohol use disorder in two adolescent cohorts.
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Bokde, Arun L W, Quinlan, Erin Burke, Desrivières Sylvane, Flor Herta, Garavan Hugh, Gowland Penny
    Abstract:

    Genetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study ( = 2,051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) ( = 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 analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP×SNP interaction of the five 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 ( < 0.05; OR

  • Endocannabinoid Gene × Gene Interaction Association to Alcohol Use Disorder in Two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Vosberg Daniel, Bokde Arun, Quinlan Erin, Gowland Penny
    Abstract:

    International audienceGenetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study (n = 2,051) 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×SNP interaction of the five 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

  • Endocannabinoid Gene x Gene Interaction Association to Alcohol Use Disorder in two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Bokde Arun, Quinlan, Erin B, Gowland Penny
    Abstract:

    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 [less than] 0.05; OR [less than] 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 [less than] 0.01; OR[less than] 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

Garavan Hugh - One of the best experts on this subject based on the ideXlab platform.

  • Endocannabinoid gene × gene interaction association to alcohol use disorder in two adolescent cohorts.
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Bokde, Arun L W, Quinlan, Erin Burke, Desrivières Sylvane, Flor Herta, Garavan Hugh, Gowland Penny
    Abstract:

    Genetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study ( = 2,051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) ( = 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 analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP×SNP interaction of the five 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 ( < 0.05; OR

  • Endocannabinoid Gene × Gene Interaction Association to Alcohol Use Disorder in Two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Vosberg Daniel, Bokde Arun, Quinlan Erin, Gowland Penny
    Abstract:

    International audienceGenetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study (n = 2,051) 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×SNP interaction of the five 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

  • Endocannabinoid Gene x Gene Interaction Association to Alcohol Use Disorder in two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Bokde Arun, Quinlan, Erin B, Gowland Penny
    Abstract:

    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 [less than] 0.05; OR [less than] 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 [less than] 0.01; OR[less than] 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

Flor Herta - One of the best experts on this subject based on the ideXlab platform.

  • Endocannabinoid gene × gene interaction association to alcohol use disorder in two adolescent cohorts.
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Bokde, Arun L W, Quinlan, Erin Burke, Desrivières Sylvane, Flor Herta, Garavan Hugh, Gowland Penny
    Abstract:

    Genetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study ( = 2,051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) ( = 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 analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP×SNP interaction of the five 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 ( < 0.05; OR

  • Endocannabinoid Gene × Gene Interaction Association to Alcohol Use Disorder in Two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Vosberg Daniel, Bokde Arun, Quinlan Erin, Gowland Penny
    Abstract:

    International audienceGenetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study (n = 2,051) 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×SNP interaction of the five 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

  • Endocannabinoid Gene x Gene Interaction Association to Alcohol Use Disorder in two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Bokde Arun, Quinlan, Erin B, Gowland Penny
    Abstract:

    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 [less than] 0.05; OR [less than] 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 [less than] 0.01; OR[less than] 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

Desrivières Sylvane - One of the best experts on this subject based on the ideXlab platform.

  • Endocannabinoid gene × gene interaction association to alcohol use disorder in two adolescent cohorts.
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Bokde, Arun L W, Quinlan, Erin Burke, Desrivières Sylvane, Flor Herta, Garavan Hugh, Gowland Penny
    Abstract:

    Genetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study ( = 2,051) and explore replication in a cohort of North American adolescents from Canadian Saguenay Youth Study (SYS) ( = 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 analysis, while considering various covariates. Generalized multifactor dimensionality reduction (GMDR) was used to analyze the most robust SNP×SNP interaction of the five 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 ( < 0.05; OR

  • Endocannabinoid Gene × Gene Interaction Association to Alcohol Use Disorder in Two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Vosberg Daniel, Bokde Arun, Quinlan Erin, Gowland Penny
    Abstract:

    International audienceGenetic markers of the endocannabinoid system have been linked to a variety of addiction-related behaviors that extend beyond cannabis use. In the current study we investigate the relationship between endocannabinoid (eCB) genetic markers and alcohol use disorder (AUD) in European adolescents (14-18 years old) followed in the IMAGEN study (n = 2,051) 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×SNP interaction of the five 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

  • Endocannabinoid Gene x Gene Interaction Association to Alcohol Use Disorder in two Adolescent Cohorts
    'Frontiers Media SA', 2021
    Co-Authors: Elkrief Laurent, Spinney Sean, Vosberg, Daniel E, Banaschewski Tobias, Desrivières Sylvane, Flor Herta, Garavan Hugh, Bokde Arun, Quinlan, Erin B, Gowland Penny
    Abstract:

    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 [less than] 0.05; OR [less than] 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 [less than] 0.01; OR[less than] 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