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Introduction to Deep Sequencing and Its Application to Drug Addiction Research with a Focus on Rare Variants

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Abstract

Through linkage analysis, candidate gene approach, and genome-wide association studies (GWAS), many genetic susceptibility factors for substance dependence have been discovered such as the alcohol dehydrogenase gene (ALDH2) for alcohol dependence (AD) and nicotinic acetylcholine receptor (nAChR) subunit variants on chromosomes 8 and 15 for nicotine dependence (ND). However, these confirmed genetic factors contribute only a small portion of the heritability responsible for each addiction. Among many potential factors, rare variants in those identified and unidentified susceptibility genes are supposed to contribute greatly to the missing heritability. Several studies focusing on rare variants have been conducted by taking advantage of next-generation sequencing technologies, which revealed that some rare variants of nAChR subunits are associated with ND in both genetic and functional studies. However, these studies investigated variants for only a small number of genes and need to be expanded to broad regions/genes in a larger population. This review presents an update on recently developed methods for rare-variant identification and association analysis and on studies focused on rare-variant discovery and function related to addictions.

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Acknowledgments

The preparation of this review was supported by NIH grant DA-012844 to MDL. The authors thank Dr. David Bronson for his excellent editing.

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Authors and Affiliations

  1. Department of Psychiatry & Neurobiology Science, University of Virginia, 1670 Discovery Drive, Suite 110, Charlottesville, VA, 22911, USA

    Shaolin Wang, Zhongli Yang & Ming D. Li

  2. Shanxi Key Laboratory of Environmental Veterinary Science, Shanxi Agricultural University, Shanxi, China

    Zhongli Yang

  3. Department of Public Health Sciences, University of Virginia, Charlottesville, VA, USA

    Jennie Z. Ma

  4. ACT Center for Tobacco Treatment, Education and Research, Department of Otolaryngology and Communicative Sciences, University of Mississippi Medical Center, Jackson, MS, USA

    Thomas J. Payne

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  1. Shaolin Wang
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  2. Zhongli Yang
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  5. Ming D. Li
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Correspondence to Ming D. Li.

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Wang, S., Yang, Z., Ma, J.Z. et al. Introduction to Deep Sequencing and Its Application to Drug Addiction Research with a Focus on Rare Variants. Mol Neurobiol 49, 601–614 (2014). https://doi.org/10.1007/s12035-013-8541-4

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  • DOI: https://doi.org/10.1007/s12035-013-8541-4

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