Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study

Autoři: Kai Xiang Lim aff001;  Frühling Rijsdijk aff001;  Saskia P. Hagenaars aff001;  Adam Socrates aff001;  Shing Wan Choi aff001;  Jonathan R. I. Coleman aff001;  Kylie P. Glanville aff001;  Cathryn M. Lewis aff001;  Jean-Baptiste Pingault aff001
Působiště autorů: Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom aff001;  Icahn School of Medicine at Mount Sinai, New York, New York, United States of America aff002;  Division of Psychology and Language Sciences, University College London, London, United Kingdom aff003
Vyšlo v časopise: Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study. PLoS Med 17(6): e1003137. doi:10.1371/journal.pmed.1003137
Kategorie: Research Article
doi: 10.1371/journal.pmed.1003137



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 × 10−35) 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.


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.

Klíčová slova:

ADHD – Bipolar disorder – Cannabis – Depression – Medical risk factors – Self harm – Schizophrenia – Suicide


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