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Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study

Genetics intersects with environmental, cultural, and social factors in the development of addictive disorders. This study reports the feasibility of whole-exome sequencing of trios (subject and two family members) to discover potential genetic variants in the development of substance use disorders...

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Autores principales: AshaRani, P. V., Amron, Syidda, Zainuldin, Noor Azizah Bte, Tohari, Sumanty, Ng, Alvin Y. J., Song, Guo, Venkatesh, Byrappa, Mathuru, Ajay S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269170/
https://www.ncbi.nlm.nih.gov/pubmed/34202351
http://dx.doi.org/10.3390/jcm10132810
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author AshaRani, P. V.
Amron, Syidda
Zainuldin, Noor Azizah Bte
Tohari, Sumanty
Ng, Alvin Y. J.
Song, Guo
Venkatesh, Byrappa
Mathuru, Ajay S.
author_facet AshaRani, P. V.
Amron, Syidda
Zainuldin, Noor Azizah Bte
Tohari, Sumanty
Ng, Alvin Y. J.
Song, Guo
Venkatesh, Byrappa
Mathuru, Ajay S.
author_sort AshaRani, P. V.
collection PubMed
description Genetics intersects with environmental, cultural, and social factors in the development of addictive disorders. This study reports the feasibility of whole-exome sequencing of trios (subject and two family members) to discover potential genetic variants in the development of substance use disorders (SUD). Family trios were recruited from the National Addictions Management Service in Singapore during the 2016–2018 period. Recruited subjects had severe alcohol use disorder (AUD) or opioid use disorder (OUD), with nicotine dependence (ND) and a family history of addictive disorders. Demographic characteristics and severity of addiction were captured. Whole-exome sequencing (WES) and analysis were performed on salivary samples collected from the trios. WES revealed variants in several genes in each individual and disruptive protein mutations in most. Variants were identified in genes previously associated with SUDs, such as Pleckstrin homology domain-containing family M member 3 (PLEKHM3), coiled-coil serine-rich protein 1 (CCSER1), LIM and calponin homology domains-containing protein 1 (LIMCH1), dynein axonemal heavy chain 8 (DNAH8), and the taste receptor type 2 member 38 (TAS2R38) involved in the perception of bitterness. The feasibility study suggests that subjects with a severe addiction profile, polysubstance use, and family history of addiction may often harbor gene variants that may predispose them to SUDs. This study could serve as a model for future precision medicine-based personalized interventional strategies for behavioral addictions and SUDs and for the discovery of potentially pathogenic genetic variants.
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spelling pubmed-82691702021-07-10 Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study AshaRani, P. V. Amron, Syidda Zainuldin, Noor Azizah Bte Tohari, Sumanty Ng, Alvin Y. J. Song, Guo Venkatesh, Byrappa Mathuru, Ajay S. J Clin Med Brief Report Genetics intersects with environmental, cultural, and social factors in the development of addictive disorders. This study reports the feasibility of whole-exome sequencing of trios (subject and two family members) to discover potential genetic variants in the development of substance use disorders (SUD). Family trios were recruited from the National Addictions Management Service in Singapore during the 2016–2018 period. Recruited subjects had severe alcohol use disorder (AUD) or opioid use disorder (OUD), with nicotine dependence (ND) and a family history of addictive disorders. Demographic characteristics and severity of addiction were captured. Whole-exome sequencing (WES) and analysis were performed on salivary samples collected from the trios. WES revealed variants in several genes in each individual and disruptive protein mutations in most. Variants were identified in genes previously associated with SUDs, such as Pleckstrin homology domain-containing family M member 3 (PLEKHM3), coiled-coil serine-rich protein 1 (CCSER1), LIM and calponin homology domains-containing protein 1 (LIMCH1), dynein axonemal heavy chain 8 (DNAH8), and the taste receptor type 2 member 38 (TAS2R38) involved in the perception of bitterness. The feasibility study suggests that subjects with a severe addiction profile, polysubstance use, and family history of addiction may often harbor gene variants that may predispose them to SUDs. This study could serve as a model for future precision medicine-based personalized interventional strategies for behavioral addictions and SUDs and for the discovery of potentially pathogenic genetic variants. MDPI 2021-06-25 /pmc/articles/PMC8269170/ /pubmed/34202351 http://dx.doi.org/10.3390/jcm10132810 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Brief Report
AshaRani, P. V.
Amron, Syidda
Zainuldin, Noor Azizah Bte
Tohari, Sumanty
Ng, Alvin Y. J.
Song, Guo
Venkatesh, Byrappa
Mathuru, Ajay S.
Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study
title Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study
title_full Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study
title_fullStr Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study
title_full_unstemmed Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study
title_short Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study
title_sort whole-exome sequencing to identify potential genetic risk in substance use disorders: a pilot feasibility study
topic Brief Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8269170/
https://www.ncbi.nlm.nih.gov/pubmed/34202351
http://dx.doi.org/10.3390/jcm10132810
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