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Human Genetics of Addiction: New Insights and Future Directions

Abstract

Purpose of Review

With the advent of the genome-wide association study (GWAS), our understanding of the genetics of addiction has made significant strides forward. Here, we summarize genetic loci containing variants identified at genome-wide statistical significance (P < 5 × 10−8) and independently replicated, review evidence of functional or regulatory effects for GWAS-identified variants, and outline multi-omics approaches to enhance discovery and characterize addiction loci.

Recent Findings

Replicable GWAS findings span 11 genetic loci for smoking, eight loci for alcohol, and two loci for illicit drugs combined and include missense functional variants and noncoding variants with regulatory effects in human brain tissues traditionally viewed as addiction-relevant (e.g., prefrontal cortex [PFC]) and, more recently, tissues often overlooked (e.g., cerebellum).

Summary

GWAS analyses have discovered several novel, replicable variants contributing to addiction. Using larger sample sizes from harmonized datasets and new approaches to integrate GWAS with multiple ‘omics data across human brain tissues holds great promise to significantly advance our understanding of the biology underlying addiction.

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Funding

This work was supported by NIDA grants R01s DA035825 and DA042090 (PI: Dana Hancock) and R01 DA036583 (PI: Laura Bierut).

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Correspondence to Dana B. Hancock.

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Conflict of Interest

Dana B. Hancock reports grants from National Institutes of Health.

Christina A. Markunas reports grants from National Institutes of Health.

Laura J. Bierut reports grants from National Institutes of Health. In addition, Dr. Bierut is listed as an inventor on U.S. Patent 8,080,371,“Markers for Addiction” covering the use of certain SNPs in determining the diagnosis, prognosis, and treatment of addiction.

Eric O. Johnson reports grants from National Institutes of Health.

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This article does not contain any studies with human or animal subjects performed by any of the authors.

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This article is part of the Topical Collection on Genetic Disorders

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Hancock, D.B., Markunas, C.A., Bierut, L.J. et al. Human Genetics of Addiction: New Insights and Future Directions. Curr Psychiatry Rep 20, 8 (2018). https://doi.org/10.1007/s11920-018-0873-3

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  • DOI: https://doi.org/10.1007/s11920-018-0873-3

Keywords

  • GWAS
  • Omics
  • Brain
  • Nicotine/smoking
  • Alcohol
  • Drugs