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Genome-wide association study of stimulant dependence
Stimulant dependence is heritable, but specific genetic factors underlying the trait have not been identified. A genome-wide association study for stimulant dependence was performed in a discovery cohort of African- (AA) and European-ancestry (EA) subjects ascertained for genetic studies of alcohol,...
Autores principales: | , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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Nature Publishing Group UK
2021
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257618/ https://www.ncbi.nlm.nih.gov/pubmed/34226506 http://dx.doi.org/10.1038/s41398-021-01440-5 |
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author | Cox, Jiayi Sherva, Richard Wetherill, Leah Foroud, Tatiana Edenberg, Howard J. Kranzler, Henry R. Gelernter, Joel Farrer, Lindsay A. |
author_facet | Cox, Jiayi Sherva, Richard Wetherill, Leah Foroud, Tatiana Edenberg, Howard J. Kranzler, Henry R. Gelernter, Joel Farrer, Lindsay A. |
author_sort | Cox, Jiayi |
collection | PubMed |
description | Stimulant dependence is heritable, but specific genetic factors underlying the trait have not been identified. A genome-wide association study for stimulant dependence was performed in a discovery cohort of African- (AA) and European-ancestry (EA) subjects ascertained for genetic studies of alcohol, opioid, and cocaine use disorders. The sample comprised individuals with DSM-IV stimulant dependence (393 EA cases, 5288 EA controls; 155 AA cases, 5603 AA controls). An independent cohort from the family-based Collaborative Study on the Genetics of Alcoholism (532 EA cases, 7635 EA controls; 53 AA cases, AA 3352 controls) was used for replication. One variant in SLC25A16 (rs2394476, p = 3.42 × 10(−10), odds ratio [OR] = 3.70) was GWS in AAs. Four other loci showed suggestive evidence, including KCNA4 in AAs (rs11500237, p = 2.99 × 10(−7), OR = 2.31) which encodes one of the potassium voltage-gated channel protein that has been linked to several other substance use disorders, and CPVL in the combined population groups (rs1176440, p = 3.05 × 10(−7), OR = 1.35), whose expression was previously shown to be upregulated in the prefrontal cortex from users of cocaine, cannabis, and phencyclidine. Analysis of the top GWAS signals revealed a significant enrichment with nicotinic acetylcholine receptor genes (adjusted p = 0.04) and significant pleiotropy between stimulant dependence and alcohol dependence in EAs (p(adj) = 3.6 × 10(−3)), an anxiety disorder in EAs (p(adj) = 2.1 × 10(−4)), and ADHD in both AAs (p(adj) = 3.0 × 10(−33)) and EAs (p(adj) = 6.7 × 10(−35)). Our results implicate novel genes and pathways as having roles in the etiology of stimulant dependence. |
format | Online Article Text |
id | pubmed-8257618 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2021 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-82576182021-07-23 Genome-wide association study of stimulant dependence Cox, Jiayi Sherva, Richard Wetherill, Leah Foroud, Tatiana Edenberg, Howard J. Kranzler, Henry R. Gelernter, Joel Farrer, Lindsay A. Transl Psychiatry Article Stimulant dependence is heritable, but specific genetic factors underlying the trait have not been identified. A genome-wide association study for stimulant dependence was performed in a discovery cohort of African- (AA) and European-ancestry (EA) subjects ascertained for genetic studies of alcohol, opioid, and cocaine use disorders. The sample comprised individuals with DSM-IV stimulant dependence (393 EA cases, 5288 EA controls; 155 AA cases, 5603 AA controls). An independent cohort from the family-based Collaborative Study on the Genetics of Alcoholism (532 EA cases, 7635 EA controls; 53 AA cases, AA 3352 controls) was used for replication. One variant in SLC25A16 (rs2394476, p = 3.42 × 10(−10), odds ratio [OR] = 3.70) was GWS in AAs. Four other loci showed suggestive evidence, including KCNA4 in AAs (rs11500237, p = 2.99 × 10(−7), OR = 2.31) which encodes one of the potassium voltage-gated channel protein that has been linked to several other substance use disorders, and CPVL in the combined population groups (rs1176440, p = 3.05 × 10(−7), OR = 1.35), whose expression was previously shown to be upregulated in the prefrontal cortex from users of cocaine, cannabis, and phencyclidine. Analysis of the top GWAS signals revealed a significant enrichment with nicotinic acetylcholine receptor genes (adjusted p = 0.04) and significant pleiotropy between stimulant dependence and alcohol dependence in EAs (p(adj) = 3.6 × 10(−3)), an anxiety disorder in EAs (p(adj) = 2.1 × 10(−4)), and ADHD in both AAs (p(adj) = 3.0 × 10(−33)) and EAs (p(adj) = 6.7 × 10(−35)). Our results implicate novel genes and pathways as having roles in the etiology of stimulant dependence. Nature Publishing Group UK 2021-06-29 /pmc/articles/PMC8257618/ /pubmed/34226506 http://dx.doi.org/10.1038/s41398-021-01440-5 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Cox, Jiayi Sherva, Richard Wetherill, Leah Foroud, Tatiana Edenberg, Howard J. Kranzler, Henry R. Gelernter, Joel Farrer, Lindsay A. Genome-wide association study of stimulant dependence |
title | Genome-wide association study of stimulant dependence |
title_full | Genome-wide association study of stimulant dependence |
title_fullStr | Genome-wide association study of stimulant dependence |
title_full_unstemmed | Genome-wide association study of stimulant dependence |
title_short | Genome-wide association study of stimulant dependence |
title_sort | genome-wide association study of stimulant dependence |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8257618/ https://www.ncbi.nlm.nih.gov/pubmed/34226506 http://dx.doi.org/10.1038/s41398-021-01440-5 |
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