- Title
- Pairwise genetic meta-analyses between schizophrenia and substance dependence phenotypes reveals novel association signals with pharmacological significance
- Creator
- Greco, Laura A.; Reay, William R.; Dayas, Christopher V.; Cairns, Murray J.
- Relation
- NHMRC.1147644 http://purl.org/au-research/grants/nhmrc/1147644 | 1121474 http://purl.org/au-research/grants/nhmrc/1121474
- Relation
- Translational Psychiatry Vol. 12, Issue 1, no. 403
- Publisher Link
- http://dx.doi.org/10.1038/s41398-022-02186-4
- Publisher
- Nature Publishing Group
- Resource Type
- journal article
- Date
- 2022
- Description
- Almost half of individuals diagnosed with schizophrenia also present with a substance use disorder, however, little is known about potential molecular mechanisms underlying this comorbidity. We used genetic analyses to enhance our understanding of the molecular overlap between these conditions. Our analyses revealed a positive genetic correlation between schizophrenia and the following dependence phenotypes: alcohol (rg = 0.368, SE = 0.076, P = 1.61 × 10−6), cannabis use disorder (rg = 0.309, SE = 0.033, P = 1.97 × 10−20) and nicotine (rg = 0.117, SE = 0.043, P = 7.0 × 10−3), as well as drinks per week (rg = 0.087, SE = 0.021, P = 6.36 × 10−5), cigarettes per day (rg = 0.11, SE = 0.024, P = 4.93 × 10−6) and life-time cannabis use (rg = 0.234, SE = 0.029, P = 3.74 × 10−15). We further constructed latent causal variable (LCV) models to test for partial genetic causality and found evidence for a potential causal relationship between alcohol dependence and schizophrenia (GCP = 0.6, SE = 0.22, P = 1.6 × 10−3). This putative causal effect with schizophrenia was not seen using a continuous phenotype of drinks consumed per week, suggesting that distinct molecular mechanisms underlying dependence are involved in the relationship between alcohol and schizophrenia. To localise the specific genetic overlap between schizophrenia and substance use disorders (SUDs), we conducted a gene-based and gene-set pairwise meta-analysis between schizophrenia and each of the four individual substance dependence phenotypes in up to 790,806 individuals. These bivariate meta-analyses identified 44 associations not observed in the individual GWAS, including five shared genes that play a key role in early central nervous system development. The results from this study further supports the existence of underlying shared biology that drives the overlap in substance dependence in schizophrenia, including specific biological systems related to metabolism and neuronal function.
- Subject
- schizophrenia; substance use; alcohol dependence; metabolism; SDG 3; Sustainable Development Goals
- Identifier
- http://hdl.handle.net/1959.13/1482452
- Identifier
- uon:50935
- Identifier
- ISSN:2158-3188
- Rights
- © The Author(s) 2022. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
- Language
- eng
- Full Text
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