Comorbidity alters the genetic relationship between anxiety disorders and major depression.
| Autor: | Tesfaye M; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Clinical Science, University of Bergen, Bergen, Norway., Shadrin A; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo and Oslo University Hospital, Oslo, Norway., Parker N; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Jaholkowski P; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Parekh P; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Kutrolli G; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Birkenæs V; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Bakken NR; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Ask H; PsychGen Center for Genetic Epidemiology and Mental Health, Norwegian Institute of Public Health, Oslo, Norway.; PROMENTA Research Center, Department of Psychology, University of Oslo, Oslo, Norway., Frei O; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Center for Bioinformatics, Department of Informatics, University of Oslo, Oslo, Norway., Djurovic S; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; Department of Medical Genetics, Oslo University Hospital, Oslo, Norway., Dale AM; Department of Radiology, University of California, San Diego, La Jolla, CA, USA.; Multimodal Imaging Laboratory, University of California San Diego, La Jolla, CA, USA.; Department of Psychiatry, University of California, San Diego, La Jolla, CA, USA.; Department of Neurosciences, University of California San Diego, La Jolla, CA, USA., Smeland OB; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., O'Connell KS; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway., Andreassen OA; Centre for Precision Psychiatry, Division of Mental Health and Addiction, Oslo University Hospital, and Institute of Clinical Medicine, University of Oslo, Oslo, Norway.; KG Jebsen Centre for Neurodevelopmental Disorders, University of Oslo and Oslo University Hospital, Oslo, Norway. |
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| Jazyk: | angličtina |
| Zdroj: | MedRxiv : the preprint server for health sciences [medRxiv] 2024 Nov 20. Date of Electronic Publication: 2024 Nov 20. |
| DOI: | 10.1101/2024.11.19.24317523 |
| Abstrakt: | Importance: There is extensive comorbidity between anxiety disorders (ANX) and major depression (MD). Most studies on the genetics of ANX do not exclude comorbid cases of MD, and vice versa , therefore confounding genetic association analyses. Disorder-specific analysis of genomic data may reveal more precise biological pathways and causal relationships. Objective: To investigate the genetic relationship between disorder-specific ANX and MD compared to samples with comorbidity, including their causal relationship. Design Setting and Participants: Data from UK Biobank was used to perform genome-wide association studies (GWAS) of ANX-only and MD-only, and generate disorder-specific polygenic risk scores (PRS). The Norwegian Mother, Father, and Child Cohort (MoBa) was used to test the associations of PRS with diagnosis and symptoms. MD and ANX GWAS data including comorbidities (MD-co and ANX-co) were used as comparators. Genetic correlation was assessed using LDSC, and Mendelian randomization was employed to infer causal relationships. Main Outcomes and Measures: GWAS of ICD-10 diagnoses of ANX, MD, or both. Genetic correlations between pairs of ANX and MD phenotypes. PRS associations with diagnoses of ANX, MD, and their comorbid states, and anxiety or depressive symptoms. Results: The GWAS of ANX-only (9,980 cases and 179,442 controls) and MD-only (15,301 cases and 179,038 controls) showed a lower genetic correlation (0.53) than the one between ANX-co and MD-co (0.90). ANX-only showed a causal relationship with MD-only (P Conclusions and Relevance: The genetics and underlying biology of ANX and MD are more distinct when comorbid cases are excluded from analyses and reveals that ANX may be causal for MD. This confounding of genetic relationships as a result of comorbidity is likely to apply to other psychiatric disorders. Disorder-specific genetic studies may help uncover more relevant biological mechanisms and guide more targeted clinical interventions. Competing Interests: Conflict of Interest Disclosures Ole A. Andreassen is a consultant for Cortechs.ai and Precision Health and has received speaker’s honoraria from Lundbeck, Janssen, Otsuka, and Sunovion. Srdjan Djurovic has received speaker’s honoraria from Lundbeck. Dr. Anders M. Dale is the Founding Director, holds equity in CorTechs Labs, Inc. (DBA Cortechs.ai), and serves on its Board of Directors and the Scientific Advisory Board. He is an unpaid consultant for Oslo University Hospital. The terms of these arrangements have been reviewed and approved by the University of California, San Diego in accordance with its conflict-of-interest policies. Dr. Frei is a consultant to Precision Health. The other authors have no conflicts of interest to declare. |
| Databáze: | MEDLINE |
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