Lim, KX; Rijsdijk, F; Hagenaars, S; Socrates, A; Choi, SW; Coleman, JRI; Glanville, K; ... Pingault, J-B; + view all Lim, KX; Rijsdijk, F; Hagenaars, S; Socrates, A; Choi, SW; Coleman, JRI; Glanville, K; Lewis, C; Pingault, J-B; - view fewer (2019) Identifying Potential Causal Risk Factors for Self-Harm: A Polygenic Risk Scoring and Mendelian Randomisation Approach. bioRxiv 10.1101/673053.

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Abstract

BACKGROUND: Multiple individual vulnerabilities and traits are phenotypically associated with suicidal and non-suicidal self-harm. However, associations between these risk factors and self-harm are subject to confounding. We implemented genetically informed methods to better identify individual risk factors for self-harm. METHODS: sing genotype data and online Mental Health Questionnaire responses in the UK Biobank sample (N = 125,925), polygenic risk scores (PRS) were generated to index 24 plausible individual risk factors for self-harm in the following domains: mental health vulnerabilities, substance use phenotypes, cognitive traits, personality traits and physical traits. PRS were entered as predictors in binomial regression models to predict self-harm. Multinomial regressions were used to model suicidal and non-suicidal self-harm. To further probe the causal nature of these relationships, two-sample Mendelian Randomisation (MR) analyses were conducted for significant risk factors identified in PRS analyses. OUTCOMES: Self-harm was predicted by PRS indexing six individual risk factors, which are major depressive disorder (MDD), attention deficit/hyperactivity disorder (ADHD), bipolar disorder, schizophrenia, alcohol dependence disorder (ALC) and lifetime cannabis use. Effect sizes ranged from β = 0.044 (95% CI: 0.016 to 0.152) for PRS for lifetime cannabis use, to β = 0.179 (95% CI: 0.152 to 0.207) for PRS for MDD. No systematic distinctions emerged between suicidal and non-suicidal self-harm. In follow-up MR analyses, MDD, ADHD and schizophrenia emerged as plausible causal risk factors for self-harm. INTERPRETATION: Among a range of potential risk factors leading to self-harm, core predictors were found among psychiatric disorders. In addition to MDD, liabilities for schizophrenia and ADHD increased the risk for self-harm. Detection and treatment of core symptoms of these conditions, such as psychotic or impulsivity symptoms, may benefit self-harming patients. FUNDING: Lim is funded by King’s International Postgraduate Research Scholarship. Dr Pingault is funded by grant MQ16IP16 from MQ: Transforming Mental Health. Dr Coleman is supported by the UK National Institute of Health Research Maudsley Biomedical Research Centre. MRC grant MR/N015746/1 to CML and PFO’R. Dr Hagenaars is funded by the Medical Research Council (MR/S0151132). Kylie P. Glanville is funded by the UK Medical Research Council (PhD studentship; grant MR/N015746/1). This paper represents independent research part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at South London and Maudsley NHS Foundation Trust and King’s College London. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR or the Department of Health and Social Care.

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