Molecular Neurobiology

, Volume 49, Issue 1, pp 601–614

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

  • Shaolin Wang
  • Zhongli Yang
  • Jennie Z. Ma
  • Thomas J. Payne
  • Ming D. Li


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.


Rare variants Next-generation sequencing Drug addiction 

Supplementary material

12035_2013_8541_MOESM1_ESM.docx (39 kb)
ESM 1(DOCX 39 kb)


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Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Shaolin Wang
    • 1
  • Zhongli Yang
    • 1
    • 2
  • Jennie Z. Ma
    • 3
  • Thomas J. Payne
    • 4
  • Ming D. Li
    • 1
  1. 1.Department of Psychiatry & Neurobiology ScienceUniversity of VirginiaCharlottesvilleUSA
  2. 2.Shanxi Key Laboratory of Environmental Veterinary ScienceShanxi Agricultural UniversityShanxiChina
  3. 3.Department of Public Health SciencesUniversity of VirginiaCharlottesvilleUSA
  4. 4.ACT Center for Tobacco Treatment, Education and Research, Department of Otolaryngology and Communicative SciencesUniversity of Mississippi Medical CenterJacksonUSA

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