Molecular genetics of substance use disorders: An umbrella review

Neurosci Biobehav Rev. 2021 May;124:358-369. doi: 10.1016/j.neubiorev.2021.01.019. Epub 2021 Feb 5.


Background: Substance use disorders (SUD) are a category of psychiatric disorders with a large epidemiological and societal impact around the world. In the last decades, a large number of genetic studies have been published for SUDs.

Methods: With the objective of having an overview and summarizing the evidence published up to date, we carried out an umbrella review of all the meta-analyses of genetic studies for the following substances: alcohol, tobacco, cannabis, cocaine, opioids, heroin and methamphetamines. Meta-analyses for candidate gene studies and genome-wide association studies (GWAS) were included.

Results: Alcohol and tobacco were the substances with the largest number of meta-analyses, and cannabis, opioids and cocaine the least studied. The following genes were associated with two or more SUDs: OPRM1, DRD2, DRD4, BDNF and SL6A4. The only genes that had an OR higher than two were the SLC6A4 for all addictions, the ADH1B for alcohol dependence, and BDNF for methamphetamine dependence. GWAS confirmed the possible role of CHRNA5 gene in nicotine dependence and identified novel candidate genes in other SUDs, such as FOXP2, PEX and, AUTS2, which need further functional analyses.

Conclusions: This umbrella review summarizes the evidence of 16 years of research on the genetics of SUDs and provides a broad and detailed overview of results from more than 150 meta-analyses for SUD. The results of this umbrella review will guide the need for future genetic studies geared toward understanding, preventing and treating SUDs.

Keywords: Addiction; Alcohol; Cannabis; Cocaine; Drug dependence; Genomic studies; Meta-analyses; Opioids and methamphetamine; Substance use disorder; Tobacco.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Alcohol Dehydrogenase
  • Alcoholism* / genetics
  • Genome-Wide Association Study
  • Humans
  • Molecular Biology
  • Serotonin Plasma Membrane Transport Proteins
  • Substance-Related Disorders* / genetics
  • Tobacco Use Disorder* / genetics


  • SLC6A4 protein, human
  • Serotonin Plasma Membrane Transport Proteins
  • ADH1B protein, human
  • Alcohol Dehydrogenase