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Brief Report

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

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Research Division, Institute of Mental Health, Singapore 539747, Singapore
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National Addictions Management Service, Institute of Mental Health, Singapore 539747, Singapore
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Institute of Molecular and Cell Biology, Singapore 138673, Singapore
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Department of Pediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119228, Singapore
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Yale-NUS College, Singapore 138610, Singapore
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Department of Physiology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 117593, Singapore
*
Authors to whom correspondence should be addressed.
Academic Editor: Carmen Mannucci
J. Clin. Med. 2021, 10(13), 2810; https://doi.org/10.3390/jcm10132810
Received: 3 May 2021 / Revised: 15 June 2021 / Accepted: 22 June 2021 / Published: 25 June 2021
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. View Full-Text
Keywords: alcohol-dependence; substance use disorders; whole-exome sequencing; cohort pilot study; family trios alcohol-dependence; substance use disorders; whole-exome sequencing; cohort pilot study; family trios
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MDPI and ACS Style

AshaRani, P.V.; Amron, S.; Zainuldin, N.A.B.; Tohari, S.; Ng, A.Y.J.; Song, G.; Venkatesh, B.; Mathuru, A.S. Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study. J. Clin. Med. 2021, 10, 2810. https://doi.org/10.3390/jcm10132810

AMA Style

AshaRani PV, Amron S, Zainuldin NAB, Tohari S, Ng AYJ, Song G, Venkatesh B, Mathuru AS. Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study. Journal of Clinical Medicine. 2021; 10(13):2810. https://doi.org/10.3390/jcm10132810

Chicago/Turabian Style

AshaRani, P. V., Syidda Amron, Noor Azizah Bte Zainuldin, Sumanty Tohari, Alvin Y. J. Ng, Guo Song, Byrappa Venkatesh, and Ajay S. Mathuru. 2021. "Whole-Exome Sequencing to Identify Potential Genetic Risk in Substance Use Disorders: A Pilot Feasibility Study" Journal of Clinical Medicine 10, no. 13: 2810. https://doi.org/10.3390/jcm10132810

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