학술논문
Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders
Document Type
Original Paper
Author
Hatoum, Alexander S.; Colbert, Sarah M. C.; Johnson, Emma C.; Huggett, Spencer B.; Deak, Joseph D.; Pathak, Gita A.; Jennings, Mariela V.; Paul, Sarah E.; Karcher, Nicole R.; Hansen, Isabella; Baranger, David A. A.; Edwards, Alexis; Grotzinger, Andrew D.; Tucker-Drob, Elliot M.; Kranzler, Henry R.; Davis, Lea K.; Sanchez-Roige, Sandra; Polimanti, Renato; Gelernter, Joel; Edenberg, Howard J.; Bogdan, Ryan; Agrawal, Arpana
Source
Nature Mental Health. 1(3):210-223
Subject
Language
English
ISSN
2731-6076
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 from 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 single-nucleotide polymorphisms were genome-wide significant (P < 5 × 10–8 ) 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 and 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.
Using a sample of more than 1 million individuals, Hatoum et al. identify genomic loci associated with general and substance-specific addiction risk.
Using a sample of more than 1 million individuals, Hatoum et al. identify genomic loci associated with general and substance-specific addiction risk.