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Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders.

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.

SUBMITTER: Hatoum AS

PROVIDER: S-EPMC10217792 | biostudies-literature | 2023 Mar

REPOSITORIES: biostudies-literature

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Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders.

Hatoum Alexander S AS Colbert Sarah M C SMC Johnson Emma C EC Huggett Spencer B SB Deak Joseph D JD Pathak Gita G Jennings Mariela V MV Paul Sarah E SE Karcher Nicole R NR Hansen Isabella I Baranger David A A DAA Edwards Alexis A Grotzinger Andrew A Tucker-Drob Elliot M EM Kranzler Henry R HR Davis Lea K LK Sanchez-Roige Sandra S Polimanti Renato R Gelernter Joel J Edenberg Howard J HJ Bogdan Ryan R Agrawal Arpana A

Nature. Mental health 20230322 3

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 <b>1,025,550</b> individuals of European descent and <b>92,630 individuals of</b> African descent. Nineteen ...[more]

PMID: 37250466

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Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders.

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Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders.

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