Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders

Barkhuizen, Wikus; Pain, Oliver; Dudbridge, Frank; Ronald, Angelica

doi:10.1038/s41398-020-0765-2

Cited by 21 publications

(21 citation statements)

References 82 publications

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“…Estimates with overlapping points are labeled for the sake of clarity. Relevant results from Barkhuizen et al 121 are not plotted, as they were not reported with standard errors in the original study, while estimates from Anttila et al 88 are excluded owing to negative standard errors being reported in the original study. A correlation matrix of all estimates is also provided in the Supplementary Material, available online.…”

Section: Discussionmentioning

confidence: 99%

Systematic Review: Molecular Studies of Common Genetic Variation in Child and Adolescent Psychiatric Disorders

Akingbuwa

Hammerschlag

Bartels

et al. 2022

Journal of the American Academy of Child & Adolescent Psych

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Objective: A systematic review of studies using molecular genetics and statistical approaches to investigate the role of common genetic variation in the development, persistence, and comorbidity of childhood psychiatric traits was conducted. Method: A literature review was performed using the PubMed database, following the Preferred Reporting Items for Meta-Analyses guidelines. There were 131 studies meeting inclusion criteria, having investigated at least one type of childhood-onset or childhood-measured psychiatric disorder or trait with the aim of identifying trait-associated common genetic variants, estimating the contribution of single nucleotide polymorphisms to the amount of variance explained (single nucleotide polymorphism heritability), investigating genetic overlap between psychiatric traits, or investigating whether the stability in traits or the association with adult traits is explained by genetic factors. Results: The first robustly associated genetic variants have started to be identified for childhood psychiatric traits. There were substantial contributions of common genetic variants to many traits, with variation in single nucleotide polymorphism heritability estimates depending on age and raters. Moreover, genetic variants also appeared to explain comorbidity as well as stability across a range of psychiatric traits in childhood and across the life span. Conclusion: Common genetic variation plays a substantial role in childhood psychiatric traits. Increased sample sizes will lead to increased power to identify genetic variants and to understand genetic architecture, which will ultimately be beneficial to targeted and prevention strategies. This can be achieved by harmonizing phenotype measurements, as is already proposed by large international consortia and by including the collection of genetic material in every study.

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Section: Discussionmentioning

confidence: 99%

Systematic Review: Molecular Studies of Common Genetic Variation in Child and Adolescent Psychiatric Disorders

Akingbuwa

Hammerschlag

Bartels

et al. 2022

Journal of the American Academy of Child & Adolescent Psych

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“…This is somewhat surprising given the known phenotypic association between psychotic experiences and psychiatric disorders 67 – 72 and could be explored further. Evidence suggests that psychotic experiences in adults have somewhat different underlying causal influences compared to psychotic experiences during adolescence 73 which may explain that lack of causal associations between smoking and psychotic experiences in later life. We also note that the GWASs on positive psychotic experiences were based on a small number of cases, which could have resulted in low power to detect causal effects in our study.…”

Section: Discussionmentioning

confidence: 99%

Genetic overlap and causal associations between smoking behaviours and mental health

Barkhuizen

Dudbridge

Ronald

2021

Sci Rep

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Cigarette smoking is a modifiable behaviour associated with mental health. We investigated the degree of genetic overlap between smoking behaviours and psychiatric traits and disorders, and whether genetic associations exist beyond genetic influences shared with confounding variables (cannabis and alcohol use, risk-taking and insomnia). Second, we investigated the presence of causal associations between smoking initiation and psychiatric traits and disorders. We found significant genetic correlations between smoking and psychiatric disorders and adult psychotic experiences. When genetic influences on known covariates were controlled for, genetic associations between most smoking behaviours and schizophrenia and depression endured (but not with bipolar disorder or most psychotic experiences). Mendelian randomization results supported a causal role of smoking initiation on psychiatric disorders and adolescent cognitive and negative psychotic experiences, although not consistently across all sensitivity analyses. In conclusion, smoking and psychiatric disorders share genetic influences that cannot be attributed to covariates such as risk-taking, insomnia or other substance use. As such, there may be some common genetic pathways underlying smoking and psychiatric disorders. In addition, smoking may play a causal role in vulnerability for mental illness.

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“…This is somewhat surprising given the known phenotypic association between PE and psychiatric disorders (84-89) and could be explored further. Evidence suggests PE in adults have somewhat different underlying causal influences to PE during adolescence (90) and this may explain that lack of causal associations of PE in later life with smoking behaviours.…”

Section: Discussionmentioning

confidence: 99%

Genetic overlap and causal associations between smoking behaviours and psychiatric traits and disorders in adolescents and adults

Barkhuizen

Dudbridge

Ronald

2020

Preprint

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Background: Epidemiological research shows that smoking is associated with psychiatric disorders and psychotic experiences, even after controlling for confounds such as cannabis use and sleep problems. We investigated degree of genetic overlap and tested for causal associations between smoking and psychiatric traits and disorders using genetic data. We tested whether genetic associations existed beyond genetic influences shared with confounding variables.Methods: Genetic correlations were estimated with LD-score regression between smoking behaviours (N=262,990-632,802) and psychiatric disorders (schizophrenia, bipolar disorder and depression; N=41,653-173,005), psychotic experiences in adolescents (N=6,297-10,098) and adults (N=116,787-117,794) and adult schizotypy (N=3,967-4,057). Genomic Structural Equation Modelling was performed to explore the associations while accounting for genetic influences of confounders (cannabis and alcohol use, risk-taking and insomnia). Causal associations were tested using Generalized Summary-based Mendelian Randomization (GSMR).Results: Significant genetic correlations were found between smoking and psychiatric disorders (rg = .10 -.38) and adult PE (rg = .33 -.40). After accounting for covarying genetic influences, genetic associations between most smoking phenotypes and schizophrenia and depression remained but not between smoking behaviours and bipolar disorder or most psychotic experiences. GSMR results supported a causal role of smoking initiation on psychiatric disorders and adolescent cognitive and negative psychotic experiences. Conclusions: Pleiotropy between smoking behaviours and schizophrenia and depressionexists beyond the common genetic basis of known confounders. Smoking also appears to be causally associated with psychiatric disorders and with cognitive PEs and negative symptoms during adolescence. Exploration of the biological links underlying smoking and psychiatric illness would be well-justified.

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Genetic overlap between psychotic experiences in the community across age and with psychiatric disorders

Cited by 21 publications

References 82 publications

Systematic Review: Molecular Studies of Common Genetic Variation in Child and Adolescent Psychiatric Disorders

Systematic Review: Molecular Studies of Common Genetic Variation in Child and Adolescent Psychiatric Disorders

Genetic overlap and causal associations between smoking behaviours and mental health

Genetic overlap and causal associations between smoking behaviours and psychiatric traits and disorders in adolescents and adults

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