Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicide.

Rona J Strawbridge,Donald M Lyall,Mark E.S Bailey,Laura M Lyall,Keira J.A Johnston,Jill P Pell,Richard J Shaw,Joey Ward,Robert Pearsall,Amy Ferguson,Claire L Niedzwiedz,Nicholas Graham,Daniel J Smith,Daniel Mackay,Breda Cullen,Julie Langan Martin

doi:10.1016/j.ebiom.2019.02.005

Rona J Strawbridge, Donald M Lyall + Show 14 more

Open Access

https://doi.org/10.1016/j.ebiom.2019.02.005

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Abstract

BackgroundSuicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic.MethodsOrdinal genome-wide association study of suicidality in the UK Biobank cohort comparing: ‘no suicidality’ controls (N = 83,557); ‘thoughts that life was not worth living’ (N = 21,063); ‘ever contemplated self-harm’ (N = 13,038); ‘act of deliberate self-harm in the past’ (N = 2498); and ‘previous suicide attempt’ (N = 2666).OutcomesWe identified three novel genome-wide significant loci for suicidality (on chromosomes nine, 11 and 13) and moderate-to-strong genetic correlations between suicidality and a range of psychiatric disorders, most notably depression (rg 0·81).InterpretationThese findings provide new information about genetic variants relating to increased risk of suicidal thoughts and behaviours. Future work should assess the extent to which polygenic risk scores for suicidality, in combination with non-genetic risk factors, may be useful for stratified approaches to suicide prevention at a population level.FundUKRI Innovation-HDR-UK Fellowship (MR/S003061/1). MRC Mental Health Data Pathfinder Award (MC_PC_17217). MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh. UKRI Innovation Fellowship (MR/R024774/1).

Highlights

Suicide is a major and growing issue for global public health
Suicidality can be considered a complex dimensional trait that fits within a Research Domain Criteria (RDoC) approach because it cuts across traditional psychiatric diagnostic classifications
A gradient of increasing suicidality was found for increasing levels of social deprivation, living alone, current or previous smoking, parental depression and chronic pain

Summary

Introduction

Suicide is a major and growing issue for global public health. ‘Suicidality’ encompasses a broad range of experiences and behaviours, from suicidal ideas/thoughts, to acts of deliberate self-harm and suicide attempts, occurring along a spectrum towards completed suicide [2]. Components of suicidal thoughts and behaviours, such as feeling that life is not worth living or contemplating self-harm, are relatively common in the general population, as well as in patients affected by a variety of separate clinical diagnoses. Suicide is a major issue for global public health. Suicidality describes a broad spectrum of thoughts and behaviours, some of which are common in the general population. MRC Doctoral Training Programme Studentship at the University of Glasgow (MR/K501335/ 1). MRC Doctoral Training Programme Studentship at the Universities of Glasgow and Edinburgh.

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