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Associations of CB1 cannabinoid receptor (CNR1) gene polymorphisms with risk for alcohol dependence: Evidence from meta-analyses of genetic and genome-wide association studies

OBJECTIVES: Reported associations of the cannabinoid receptor 1 (CNR1) single nucleotide polymorphisms (SNPs) with alcohol dependence (AD) have been inconsistent, prompting a meta-analysis to obtain more precise estimates. METHODS: A Boolean search of 4 databases (PubMed, Scopus, Google Scholar, and...

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Autores principales: Pabalan, Noel, Chaweeborisuit, Phanthip, Tharabenjasin, Phuntila, Tasanarong, Adis, Jarjanazi, Hamdi, Eiamsitrakoon, Thanee, Tapanadechopone, Pairath
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556036/
https://www.ncbi.nlm.nih.gov/pubmed/34713823
http://dx.doi.org/10.1097/MD.0000000000027343
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author Pabalan, Noel
Chaweeborisuit, Phanthip
Tharabenjasin, Phuntila
Tasanarong, Adis
Jarjanazi, Hamdi
Eiamsitrakoon, Thanee
Tapanadechopone, Pairath
author_facet Pabalan, Noel
Chaweeborisuit, Phanthip
Tharabenjasin, Phuntila
Tasanarong, Adis
Jarjanazi, Hamdi
Eiamsitrakoon, Thanee
Tapanadechopone, Pairath
author_sort Pabalan, Noel
collection PubMed
description OBJECTIVES: Reported associations of the cannabinoid receptor 1 (CNR1) single nucleotide polymorphisms (SNPs) with alcohol dependence (AD) have been inconsistent, prompting a meta-analysis to obtain more precise estimates. METHODS: A Boolean search of 4 databases (PubMed, Scopus, Google Scholar, and Mednar) sought articles that evaluated the association between CNR1 polymorphisms and risk of AD. We selected the articles with sufficient genotype frequency data to enable calculation of odds ratios (ORs) and 95% confidence intervals (CIs). Using the Population Intervention Comparators Outcome elements, AD patients (P) were compared by genotype data between AD-participants (I) and non-AD-participants (C) in order to determine the risk of AD (O) attributed to the CNR1 SNPs. Analyzing 4 SNPs (rs1049353, rs1535255, rs2023239, and rs806379) using standard genetic models, we examined associations where multiple comparisons were Holm–Bonferroni corrected. The pooled ORs were assessed for aggregate statistical power and robustness (sensitivity analysis). Subgroups were Caucasians and African-Americans. RESULTS: From 32 comparisons, 14 were significant indicating increased risk, from which 5 outcomes (P-value for association [P(a)] = .003 to <.001) survived the Holm–Bonferroni-correction, which were deemed robust. In the rs1535255 outcomes, the codominant effect (OR = 1.43, 95% CIs = 1.24–1.65, P(a) < .001) had greater statistical power than the dominant effect (OR = 1.30, 95% CI = 1.08–1.57, P(a) = .006). In contrast, the rs2023239 codominant outcome was underpowered. Significance of both rs806379 Caucasian outcomes (ORs = 1.20–1.43, 95% CIs = 1.07–1.57, P(a) = .003) contrasted with the null effects in African-Americans (ORs = 0.98–1.08, 95% CIs = 0.70–1.53). CONCLUSIONS: Three CNR1 SNPs (rs1535255, rs2023239, and rs806379) were implicated in their associations with development of AD: based on aggregate statistical power, rs1535255 presented greater evidence for associations than rs2023239; rs806379 implicated the Caucasian subgroup. Multiple statistical and meta-analytical features (consistency, robustness, and high significance) underpinned the strengths of these outcomes. Our findings could render the CNR1 polymorphisms useful in the clinical genetics of AD.
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spelling pubmed-85560362021-11-01 Associations of CB1 cannabinoid receptor (CNR1) gene polymorphisms with risk for alcohol dependence: Evidence from meta-analyses of genetic and genome-wide association studies Pabalan, Noel Chaweeborisuit, Phanthip Tharabenjasin, Phuntila Tasanarong, Adis Jarjanazi, Hamdi Eiamsitrakoon, Thanee Tapanadechopone, Pairath Medicine (Baltimore) 6600 OBJECTIVES: Reported associations of the cannabinoid receptor 1 (CNR1) single nucleotide polymorphisms (SNPs) with alcohol dependence (AD) have been inconsistent, prompting a meta-analysis to obtain more precise estimates. METHODS: A Boolean search of 4 databases (PubMed, Scopus, Google Scholar, and Mednar) sought articles that evaluated the association between CNR1 polymorphisms and risk of AD. We selected the articles with sufficient genotype frequency data to enable calculation of odds ratios (ORs) and 95% confidence intervals (CIs). Using the Population Intervention Comparators Outcome elements, AD patients (P) were compared by genotype data between AD-participants (I) and non-AD-participants (C) in order to determine the risk of AD (O) attributed to the CNR1 SNPs. Analyzing 4 SNPs (rs1049353, rs1535255, rs2023239, and rs806379) using standard genetic models, we examined associations where multiple comparisons were Holm–Bonferroni corrected. The pooled ORs were assessed for aggregate statistical power and robustness (sensitivity analysis). Subgroups were Caucasians and African-Americans. RESULTS: From 32 comparisons, 14 were significant indicating increased risk, from which 5 outcomes (P-value for association [P(a)] = .003 to <.001) survived the Holm–Bonferroni-correction, which were deemed robust. In the rs1535255 outcomes, the codominant effect (OR = 1.43, 95% CIs = 1.24–1.65, P(a) < .001) had greater statistical power than the dominant effect (OR = 1.30, 95% CI = 1.08–1.57, P(a) = .006). In contrast, the rs2023239 codominant outcome was underpowered. Significance of both rs806379 Caucasian outcomes (ORs = 1.20–1.43, 95% CIs = 1.07–1.57, P(a) = .003) contrasted with the null effects in African-Americans (ORs = 0.98–1.08, 95% CIs = 0.70–1.53). CONCLUSIONS: Three CNR1 SNPs (rs1535255, rs2023239, and rs806379) were implicated in their associations with development of AD: based on aggregate statistical power, rs1535255 presented greater evidence for associations than rs2023239; rs806379 implicated the Caucasian subgroup. Multiple statistical and meta-analytical features (consistency, robustness, and high significance) underpinned the strengths of these outcomes. Our findings could render the CNR1 polymorphisms useful in the clinical genetics of AD. Lippincott Williams & Wilkins 2021-10-29 /pmc/articles/PMC8556036/ /pubmed/34713823 http://dx.doi.org/10.1097/MD.0000000000027343 Text en Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial License 4.0 (CCBY-NC), where it is permissible to download, share, remix, transform, and buildup the work provided it is properly cited. The work cannot be used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc/4.0 (https://creativecommons.org/licenses/by-nc/4.0/)
spellingShingle 6600
Pabalan, Noel
Chaweeborisuit, Phanthip
Tharabenjasin, Phuntila
Tasanarong, Adis
Jarjanazi, Hamdi
Eiamsitrakoon, Thanee
Tapanadechopone, Pairath
Associations of CB1 cannabinoid receptor (CNR1) gene polymorphisms with risk for alcohol dependence: Evidence from meta-analyses of genetic and genome-wide association studies
title Associations of CB1 cannabinoid receptor (CNR1) gene polymorphisms with risk for alcohol dependence: Evidence from meta-analyses of genetic and genome-wide association studies
title_full Associations of CB1 cannabinoid receptor (CNR1) gene polymorphisms with risk for alcohol dependence: Evidence from meta-analyses of genetic and genome-wide association studies
title_fullStr Associations of CB1 cannabinoid receptor (CNR1) gene polymorphisms with risk for alcohol dependence: Evidence from meta-analyses of genetic and genome-wide association studies
title_full_unstemmed Associations of CB1 cannabinoid receptor (CNR1) gene polymorphisms with risk for alcohol dependence: Evidence from meta-analyses of genetic and genome-wide association studies
title_short Associations of CB1 cannabinoid receptor (CNR1) gene polymorphisms with risk for alcohol dependence: Evidence from meta-analyses of genetic and genome-wide association studies
title_sort associations of cb1 cannabinoid receptor (cnr1) gene polymorphisms with risk for alcohol dependence: evidence from meta-analyses of genetic and genome-wide association studies
topic 6600
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8556036/
https://www.ncbi.nlm.nih.gov/pubmed/34713823
http://dx.doi.org/10.1097/MD.0000000000027343
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