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Background Identifying causal risk factors for self-harm is essential to inform preventive interventions. Epidemiological studies have identified risk factors associated with self-harm, but these associations can be subject to confounding. By implementing genetically informed methods to better account for confounding, this study aimed to better identify plausible causal risk factors for self-harm. Methods and findings Using summary statistics from 24 genome-wide association studies (GWASs) comprising 16,067 to 322,154 individuals, polygenic scores (PSs) were generated to index 24 possible individual risk factors for self-harm (i.e., mental health vulnerabilities, substance use, cognitive traits, personality traits, and physical traits) among a subset of UK Biobank participants (N = 125,925, 56.2% female) who completed an online mental health questionnaire in the period from 13 July 2016 to 27 July 2017. In total, 5,520 (4.4%) of these participants reported having self-harmed in their lifetime. In binomial regression models, PSs indexing 6 risk factors (major depressive disorder [MDD], attention deficit/hyperactivity disorder [ADHD], bipolar disorder, schizophrenia, alcohol dependence disorder, and lifetime cannabis use) predicted self-harm, with effect sizes ranging from odds ratio (OR) = 1.05 (95% CI 1.02 to 1.07, q = 0.008) for lifetime cannabis use to OR = 1.20 (95% CI 1.16 to 1.23, q = 1.33 x 10.sup.-35) for MDD. No systematic differences emerged between suicidal and non-suicidal self-harm. To further probe causal relationships, two-sample Mendelian randomisation (MR) analyses were conducted, with MDD, ADHD, and schizophrenia emerging as the most plausible causal risk factors for self-harm. The genetic liabilities for MDD and schizophrenia were associated with self-harm independently of diagnosis and medication. Main limitations include the lack of representativeness of the UK Biobank sample, that self-harm was self-reported, and the limited power of some of the included GWASs, potentially leading to possible type II error. Conclusions In addition to confirming the role of MDD, we demonstrate that ADHD and schizophrenia likely play a role in the aetiology of self-harm using multivariate genetic designs for causal inference. Among the many individual risk factors we simultaneously considered, our findings suggest that systematic detection and treatment of core psychiatric symptoms, including psychotic and impulsivity symptoms, may be beneficial among people at risk for self-harm., Author(s): Kai Xiang Lim 1, Frühling Rijsdijk 1, Saskia P. Hagenaars 1, Adam Socrates 1, Shing Wan Choi 1,2, Jonathan R. I. Coleman 1, Kylie P. Glanville 1, Cathryn M. [...]

Objective: The disruption caused by the COVID‐19 pandemic has been associated with poor mental health, including increases in eating disorders and self‐harm symptoms. We investigated risk and protective factors for the new onset of these symptoms during the pandemic. Method: Data were from the COVID‐19 Psychiatry and Neurological Genetics study and the Repeated Assessment of Mental health in Pandemics Study (n = 36,715). Exposures were socio‐demographic characteristics, lifetime psychiatric disorder, and COVID‐related variables, including SARS‐CoV‐2 infection/illness with COVID‐19. We identified four subsamples of participants without pre‐pandemic experience of our outcomes: binge eating (n = 24,211), low weight (n = 24,364), suicidal and/or self‐harm ideation (n = 18,040), and self‐harm (n = 29,948). Participants reported on our outcomes at frequent intervals (fortnightly to monthly). We fitted multiple logistic regression models to identify factors associated with the new onset of our outcomes. Results: Within each subsample, new onset was reported by: 21% for binge eating, 10.8% for low weight, 23.5% for suicidal and/or self‐harm ideation, and 3.5% for self‐harm. Shared risk factors included having a lifetime psychiatric disorder, not being in paid employment, higher pandemic worry scores, and being racially minoritized. Conversely, infection with SARS‐CoV‐2/illness with COVID‐19 was linked to lower odds of binge eating, low weight, and suicidal and/or self‐harm ideation. Discussion: Overall, we detected shared risk factors that may drive the comorbidity between eating disorders and self‐harm. Subgroups of individuals with these risk factors may require more frequent monitoring during future pandemics. Public Significance: In a sample of 35,000 UK residents, people who had a psychiatric disorder, identified as being part of a racially minoritized group, were not in paid employment, or were more worried about the pandemic were more likely to experience binge eating, low weight, suicidal and/or self‐harm ideation, and self‐harm for the first time during the pandemic. People with these risk factors may need particular attention during future pandemics to enable early identification of new psychiatric symptoms. [ABSTRACT FROM AUTHOR]