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Childhood trauma, life-time self-harm, and suicidal behaviour and ideation are associated with polygenic scores for autism.

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Warrier, Varun 


Autistic individuals experience significantly elevated rates of childhood trauma, self-harm and suicidal behaviour and ideation (SSBI). Is this purely the result of negative environmental experiences, or does this interact with genetic predisposition? In this study we investigated if a genetic predisposition for autism is associated with childhood trauma using polygenic scores (PGS) and genetic correlations in the UK Biobank (105,222 < N < 105,638), and tested potential mediators and moderators of the association between autism, childhood trauma and SSBI. Autism PGS were significantly associated with childhood trauma (max R2 = 0.096%, P < 2 × 10-16), self-harm ideation (max R2 = 0.108%, P < 2 × 10-16), and self-harm (max R2 = 0.13%, P < 2 × 10-16). Supporting this, we identified significant genetic correlations between autism and childhood trauma (rg = 0.36 ± 0.05, P = 8.13 × 10-11), self-harm ideation (rg = 0.49 ± 0.05, P = 4.17 × 10-21) and self-harm (rg = 0.48 ± 0.05, P = 4.58 × 10-21), and an over-transmission of PGS for the two SSBI phenotypes from parents to autistic probands. Male sex negatively moderated the effect of autism PGS on childhood trauma (β = -0.023 ± 0.005, P = 6.74 × 10-5). Further, childhood trauma positively moderated the effect of autism PGS on self-harm score (β = 8.37 × 10-3 ± 2.76 × 10-3, P = 2.42 × 10-3) and self-harm ideation (β = 7.47 × 10-3 ± 2.76 × 10-3, P = 6.71 × 10-3). Finally, depressive symptoms, quality and frequency of social interactions, and educational attainment were significant mediators of the effect of autism PGS on SSBI, with the proportion of effect mediated ranging from 0.23 (95% CI: 0.09-0.32) for depression to 0.008 (95% CI: 0.004-0.01) for educational attainment. Our findings identify that a genetic predisposition for autism is associated with adverse life-time outcomes, which represent complex gene-environment interactions, and prioritizes potential mediators and moderators of this shared biology. It is important to identify sources of trauma for autistic individuals in order to reduce their occurrence and impact.



Autistic Disorder, Genetic Predisposition to Disease, Humans, Male, Multifactorial Inheritance, Risk Factors, Self-Injurious Behavior, Suicidal Ideation

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Mol Psychiatry

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Springer Science and Business Media LLC


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Wellcome Trust (091774/Z/10/Z)
This study was funded by grants from the Medical Research Council, the Wellcome Trust, the Autism Research Trust, and the Templeton World Charity Foundation. The research was conducted in association with the National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre, and the NIHR Collaboration for Leadership in Applied Health Research and Care East of England at Cambridgeshire and Peterborough NHS Foundation Trust. The views expressed are those of the author(s) and not necessarily those of the National Health Service, the NIHR, or the Department of Health and Social Care. This research was possible due to two applications to the UK Biobank: Projects 20904 and 23787. The project leading to this application has received funding from the Innovative Medicines Initiative 2 Joint Undertaking (JU) under grant agreement No 777394. The JU receives support from the European Union’s Horizon 2020 research and innovation programme and EFPIA and AUTISM SPEAKS, Autistica, SFARI.