| Title: |
Multivariate genome-wide association meta-analysis of over 1 million subjects identifies loci underlying multiple substance use disorders |
| Authors: |
Hatoum, Alexander S; Colbert, Sarah MC; 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 AA; 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, vol 1, iss 3 |
| Publisher Information: |
eScholarship, University of California |
| Publication Year: |
2023 |
| Collection: |
University of California: eScholarship |
| Subject Terms: |
31 Biological Sciences (for-2020); 32 Biomedical and Clinical Sciences (for-2020); 3105 Genetics (for-2020); 5202 Biological Psychology (for-2020); 52 Psychology (for-2020); 3214 Pharmacology and Pharmaceutical Sciences (for-2020); Behavioral and Social Science (rcdc); Minority Health (rcdc); Opioids (rcdc); Human Genome (rcdc); Opioid Misuse and Addiction (rcdc); Alcoholism; Alcohol Use and Health (rcdc); Tobacco (rcdc); Drug Abuse (NIDA only) (rcdc); Clinical Research (rcdc); Brain Disorders (rcdc); Cannabinoid Research (rcdc); Mental Health (rcdc); Health Disparities (rcdc); Substance Misuse (rcdc); Prevention (rcdc); Genetics (rcdc); Women's Health (rcdc); 2.1 Biological and endogenous factors (hrcs-rac); Mental health (hrcs-hc); 3 Good Health and Well Being (sdg); Substance Use Disorder Working Group of the Psychiatric Genomics Consortium |
| Subject Geographic: |
210 - 223 |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
unknown |
| Relation: |
qt8b8270hc; https://escholarship.org/uc/item/8b8270hc |
| DOI: |
10.1038/s44220-023-00034-y |
| Availability: |
https://escholarship.org/uc/item/8b8270hc; https://doi.org/10.1038/s44220-023-00034-y |
| Rights: |
public |
| Accession Number: |
edsbas.6B37E904 |
| Database: |
BASE |