Cross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking.
| Title: | Cross-ancestry genetic investigation of schizophrenia, cannabis use disorder, and tobacco smoking. |
|---|---|
| Authors: | Johnson EC; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. emma.c.johnson@wustl.edu.; Austin-Zimmerman I; Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.; Thorpe HHA; Department of Anatomy and Cell Biology, Western University, London, ON, Canada.; Levey DF; Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.; Baranger DAA; Department of Psychological and Brain Sciences, Washington University in Saint Louis, St. Louis, MO, USA.; Colbert SMC; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY, USA.; Demontis D; The Lundbeck Foundation Initiative for Integrative Psychiatric Research (iPSYCH), Aarhus, Denmark.; Department of Biomedicine and Centre for Integrative Sequencing (iSEQ), Aarhus University, Aarhus, Denmark.; Khokhar JY; Department of Anatomy and Cell Biology, Western University, London, ON, Canada.; Davis LK; Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA.; Department of Psychiatry and Behavioral Sciences, Vanderbilt University Medical Center, Nashville, TN, USA.; Department of Biomedical Informatics, Vanderbilt University Medical Center, Nashville, TN, USA.; Edenberg HJ; Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.; Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA.; Di Forti M; Social, Genetic, and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, UK.; Sanchez-Roige S; Department of Medicine, Division of Genetic Medicine, Vanderbilt University, Nashville, TN, USA.; Department of Psychiatry, UC San Diego School of Medicine, La Jolla, CA, USA.; Gelernter J; Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.; Department of Psychiatry, Veterans Affairs Connecticut Healthcare Center, West Haven, CT, USA.; Agrawal A; Department of Psychiatry, Washington University School of Medicine, St. Louis, MO, USA. |
| Source: | Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology [Neuropsychopharmacology] 2024 Oct; Vol. 49 (11), pp. 1655-1665. Date of Electronic Publication: 2024 Jun 21. |
| Publication Type: | Journal Article |
| Language: | English |
| Journal Info: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 8904907 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1740-634X (Electronic) Linking ISSN: 0893133X NLM ISO Abbreviation: Neuropsychopharmacology Subsets: MEDLINE |
| Imprint Name(s): | Publication: 2003- : London : Nature Publishing Group; Original Publication: [New York, NY] : Elsevier, [c1987- |
| MeSH Terms: | Marijuana Abuse*/genetics ; Schizophrenia*/genetics ; Tobacco Smoking*/genetics; Black People/genetics ; White People/genetics ; Humans ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Polymorphism, Single Nucleotide |
| Abstract: | Individuals with schizophrenia frequently experience co-occurring substance use, including tobacco smoking and heavy cannabis use, and substance use disorders. There is interest in understanding the extent to which these relationships are causal, and to what extent shared genetic factors play a role. We explored the relationships between schizophrenia (Scz; European ancestry N = 161,405; African ancestry N = 15,846), cannabis use disorder (CanUD; European ancestry N = 886,025; African ancestry N = 120,208), and ever-regular tobacco smoking (Smk; European ancestry N = 805,431; African ancestry N = 24,278) using the largest available genome-wide studies of these phenotypes in individuals of African and European ancestries. All three phenotypes were positively genetically correlated (rgs = 0.17-0.62). Genetic instrumental variable analyses suggested the presence of shared heritable factors, but evidence for bidirectional causal relationships was also found between all three phenotypes even after correcting for these shared genetic factors. We identified 327 pleiotropic loci with 439 lead SNPs in the European ancestry data, 150 of which were novel (i.e., not genome-wide significant in the original studies). Of these pleiotropic loci, 202 had lead variants which showed convergent effects (i.e., same direction of effect) on Scz, CanUD, and Smk. Genetic variants convergent across all three phenotypes showed strong genetic correlations with risk-taking, executive function, and several mental health conditions. Our results suggest that both shared genetic factors and causal mechanisms may play a role in the relationship between CanUD, Smk, and Scz, but longitudinal, prospective studies are needed to confirm a causal relationship.; (© 2024. The Author(s).) |
| Comments: | Update of: medRxiv. 2024 Jan 18:2024.01.17.24301430. doi: 10.1101/2024.01.17.24301430.. (PMID: 38293235) |
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| Grant Information: | 1IK2BX005058-01A2 U.S. Department of Veterans Affairs (Department of Veterans Affairs); K01 DA051759 United States DA NIDA NIH HHS; DP1 DA054394 United States DA NIDA NIH HHS; Canada Research Chair in Translational Neuropsychopharmacology Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); K99AA030808 U.S. Department of Health & Human Services | NIH | National Institute on Alcohol Abuse and Alcoholism (NIAAA); IK2 BX005058 United States BX BLRD VA; Postdoctoral Fellowship Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada); K99 AA030808 United States AA NIAAA NIH HHS; UL1 TR001863 United States TR NCATS NIH HHS; R01DA058862 U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA); R01 DA058862 United States DA NIDA NIH HHS; K01DA051759 U.S. Department of Health & Human Services | NIH | National Institute on Drug Abuse (NIDA) |
| Entry Date(s): | Date Created: 20240621 Date Completed: 20240913 Latest Revision: 20260306 |
| Update Code: | 20260306 |
| PubMed Central ID: | PMC11399264 |
| DOI: | 10.1038/s41386-024-01886-3 |
| PMID: | 38906991 |
| Database: | MEDLINE |
Journal Article