Multivariate Genome-Wide Association Meta-Analysis of Over 1 Million Subjects Identifies Loci Underlying Multiple Substance Use Disorders

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Citation

Hatoum, Alexander S.; Colbert, Sarah M. C.; Johnson, Emma C.; Huggett, Spencer B.; Deak, Joseph D.; Pathak, Gita; Jennings, Mariela V.; Paul, Sarah E.; Karcher, Nicole R.; & Hansen, Isabella, et al. (2023). Multivariate Genome-Wide Association Meta-Analysis of Over 1 Million Subjects Identifies Loci Underlying Multiple Substance Use Disorders. Nature Mental Health, 1(3), 210-223. PMCID: PMC10217792

Abstract

Genetic liability to substance use disorders can be parsed into loci that confer general or substance-specific addiction risk. We report a multivariate genome-wide association meta-analysis that disaggregates general and substance-specific loci for published summary statistics of problematic alcohol use, problematic tobacco use, cannabis use disorder, and opioid use disorder in a sample of 1,025,550 individuals of European descent and 92,630 individuals of African descent. Nineteen independent SNPs were genome-wide significant (P < 5e-8) for the general addiction risk factor (addiction-rf), which showed high polygenicity. Across ancestries, PDE4B was significant (among other genes), suggesting dopamine regulation as a cross-substance vulnerability. An addiction-rf polygenic risk score was associated with substance use disorders, psychopathologies, somatic conditions, and environments associated with the onset of addictions. Substance-specific loci (9 for alcohol, 32 for tobacco, 5 for cannabis, 1 for opioids) included metabolic and receptor genes. These findings provide insight into genetic risk loci for substance use disorders that could be leveraged as treatment targets.

URL

http://dx.doi.org/10.1038/s44220-023-00034-y

Reference Type

Journal Article

Year Published

2023

Journal Title

Nature Mental Health

Author(s)

Hatoum, Alexander S.
Colbert, Sarah M. C.
Johnson, Emma C.
Huggett, Spencer B.
Deak, Joseph D.
Pathak, Gita
Jennings, Mariela V.
Paul, Sarah E.
Karcher, Nicole R.
Hansen, Isabella
Baranger, David A. A.
Edwards, Alexis C.
Grotzinger, Andrew D.
Substance Use Disorder Working Group of the Psychiatric Genomics Consortium [
Kathleen Mullan Harris
, member],
Tucker-Drob, Elliot M.
Kranzler, Henry R.
Davis, Lea K.
Sanchez-Roige, Sandra
Polimanti, Renato
Gelernter, Joel E.
Edenberg, Howard J.
Bogdan, Ryan
Agrawal, Arpana

Article Type

Regular

PMCID

PMC10217792

Data Set/Study

National Longitudinal Study of Adolescent to Adult Health (Add Health)

Continent/Country

United States

State

Nonspecific

Race/Ethnicity

European Ancestry
African Ancestry

ORCiD

Harris, KM - 0000-0001-9757-1026