The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling study
Background: Suicidal behaviour (SB) refers to behaviours, ranging from non-fatal suicidal behaviour, such as suicidal ideation and attempt, to completed suicide. Despite recent advancements in genomic technology and statistical methods, it is unclear to what extent the spectrum of suicidal behaviour...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-03-01
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| Series: | Frontiers in Genetics |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fgene.2023.1083969/full |
| _version_ | 1811158934199730176 |
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| author | Tahira Kootbodien Leslie London Lorna J. Martin Joel Defo Raj Ramesar |
| author_facet | Tahira Kootbodien Leslie London Lorna J. Martin Joel Defo Raj Ramesar |
| author_sort | Tahira Kootbodien |
| collection | DOAJ |
| description | Background: Suicidal behaviour (SB) refers to behaviours, ranging from non-fatal suicidal behaviour, such as suicidal ideation and attempt, to completed suicide. Despite recent advancements in genomic technology and statistical methods, it is unclear to what extent the spectrum of suicidal behaviour is explained by shared genetic aetiology.Methods: We identified nine genome-wide association statistics of suicidal behaviour (sample sizes, n, ranging from 62,648 to 125,844), ten psychiatric traits [n up to 386,533] and collectively, nine summary datasets of anthropometric, behavioural and socioeconomic-related traits [n ranging from 58,610 to 941,280]. We calculated the genetic correlation among these traits and modelled this using genomic structural equation modelling, identified shared biological processes and pathways between suicidal behaviour and psychiatric disorders and evaluated potential causal associations using Mendelian randomisation.Results: Among populations of European ancestry, we observed strong positive genetic correlations between suicide ideation, attempt and self-harm (rg range, 0.71–1.09) and moderate to strong genetic correlations between suicidal behaviour traits and a range of psychiatric disorders, most notably, major depression disorder (rg = 0.86, p = 1.62 × 10−36). Multivariate analysis revealed a common factor structure for suicidal behaviour traits, major depression, attention deficit hyperactivity disorder (ADHD) and alcohol use disorder. The derived common factor explained 38.7% of the shared variance across the traits. We identified 2,951 genes and 98 sub-network hub genes associated with the common factor, including pathways associated with developmental biology, signal transduction and RNA degradation. We found suggestive evidence for the protective effects of higher household income level on suicide attempt [OR = 0.55 (0.44–0.70), p = 1.29 × 10−5] and while further investigation is needed, a nominal significant effect of smoking on suicide attempt [OR = 1.24 (1.04–1.44), p = 0.026].Conclusion: Our findings provide evidence of shared aetiology between suicidal behaviour and psychiatric disorders and indicate potential common molecular mechanisms contributing to the overlapping pathophysiology. These findings provide a better understanding of the complex genetic architecture of suicidal behaviour and have implications for the prevention and treatment of suicidal behaviour. |
| first_indexed | 2024-04-10T05:32:42Z |
| format | Article |
| id | doaj.art-be1a34625e624610bbc1f97e0197f56c |
| institution | Directory Open Access Journal |
| issn | 1664-8021 |
| language | English |
| last_indexed | 2024-04-10T05:32:42Z |
| publishDate | 2023-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Genetics |
| spelling | doaj.art-be1a34625e624610bbc1f97e0197f56c2023-03-07T05:32:54ZengFrontiers Media S.A.Frontiers in Genetics1664-80212023-03-011410.3389/fgene.2023.10839691083969The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling studyTahira Kootbodien0Leslie London1Lorna J. Martin2Joel Defo3Raj Ramesar4UCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town and Affiliated Hospitals, Cape Town, South AfricaSchool of Public Health and Family Medicine, University of Cape Town, Cape Town, South AfricaDivision of Forensic Medicine and Toxicology, Department of Pathology, University of Cape Town, Cape Town, South AfricaUCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town and Affiliated Hospitals, Cape Town, South AfricaUCT/MRC Genomic and Precision Medicine Research Unit, Division of Human Genetics, Department of Pathology, Institute for Infectious Diseases and Molecular Medicine, University of Cape Town and Affiliated Hospitals, Cape Town, South AfricaBackground: Suicidal behaviour (SB) refers to behaviours, ranging from non-fatal suicidal behaviour, such as suicidal ideation and attempt, to completed suicide. Despite recent advancements in genomic technology and statistical methods, it is unclear to what extent the spectrum of suicidal behaviour is explained by shared genetic aetiology.Methods: We identified nine genome-wide association statistics of suicidal behaviour (sample sizes, n, ranging from 62,648 to 125,844), ten psychiatric traits [n up to 386,533] and collectively, nine summary datasets of anthropometric, behavioural and socioeconomic-related traits [n ranging from 58,610 to 941,280]. We calculated the genetic correlation among these traits and modelled this using genomic structural equation modelling, identified shared biological processes and pathways between suicidal behaviour and psychiatric disorders and evaluated potential causal associations using Mendelian randomisation.Results: Among populations of European ancestry, we observed strong positive genetic correlations between suicide ideation, attempt and self-harm (rg range, 0.71–1.09) and moderate to strong genetic correlations between suicidal behaviour traits and a range of psychiatric disorders, most notably, major depression disorder (rg = 0.86, p = 1.62 × 10−36). Multivariate analysis revealed a common factor structure for suicidal behaviour traits, major depression, attention deficit hyperactivity disorder (ADHD) and alcohol use disorder. The derived common factor explained 38.7% of the shared variance across the traits. We identified 2,951 genes and 98 sub-network hub genes associated with the common factor, including pathways associated with developmental biology, signal transduction and RNA degradation. We found suggestive evidence for the protective effects of higher household income level on suicide attempt [OR = 0.55 (0.44–0.70), p = 1.29 × 10−5] and while further investigation is needed, a nominal significant effect of smoking on suicide attempt [OR = 1.24 (1.04–1.44), p = 0.026].Conclusion: Our findings provide evidence of shared aetiology between suicidal behaviour and psychiatric disorders and indicate potential common molecular mechanisms contributing to the overlapping pathophysiology. These findings provide a better understanding of the complex genetic architecture of suicidal behaviour and have implications for the prevention and treatment of suicidal behaviour.https://www.frontiersin.org/articles/10.3389/fgene.2023.1083969/fullpsychiastric disordersgenomic structural equation modelingGWAS-genome-wide association studysuicidal behavior (SB)genetic correlationmendelian randomization |
| spellingShingle | Tahira Kootbodien Leslie London Lorna J. Martin Joel Defo Raj Ramesar The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling study Frontiers in Genetics psychiastric disorders genomic structural equation modeling GWAS-genome-wide association study suicidal behavior (SB) genetic correlation mendelian randomization |
| title | The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling study |
| title_full | The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling study |
| title_fullStr | The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling study |
| title_full_unstemmed | The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling study |
| title_short | The shared genetic architecture of suicidal behaviour and psychiatric disorders: A genomic structural equation modelling study |
| title_sort | shared genetic architecture of suicidal behaviour and psychiatric disorders a genomic structural equation modelling study |
| topic | psychiastric disorders genomic structural equation modeling GWAS-genome-wide association study suicidal behavior (SB) genetic correlation mendelian randomization |
| url | https://www.frontiersin.org/articles/10.3389/fgene.2023.1083969/full |
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