Identification of novel genome-wide associations for suicidality in UK Biobank, genetic correlation with psychiatric disorders and polygenic association with completed suicideResearch in context
Rona J. Strawbridge,
Joey Ward,
Amy Ferguson,
Nicholas Graham,
Richard J. Shaw,
Breda Cullen,
Robert Pearsall,
Laura M. Lyall,
Keira J.A. Johnston,
Claire L. Niedzwiedz,
Jill P. Pell,
Daniel Mackay,
Julie Langan Martin,
Donald M. Lyall,
Mark E.S. Bailey,
Daniel J. Smith
Affiliations
Rona J. Strawbridge
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; Department of Medicine Solna, Karolinska Institute, Stockholm, Sweden
Joey Ward
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Amy Ferguson
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Nicholas Graham
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Richard J. Shaw
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Breda Cullen
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Robert Pearsall
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Laura M. Lyall
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Keira J.A. Johnston
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; Division of Psychiatry, College of Medicine, University of Edinburgh, UK; School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
Claire L. Niedzwiedz
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Jill P. Pell
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Daniel Mackay
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Julie Langan Martin
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Donald M. Lyall
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK
Mark E.S. Bailey
School of Life Sciences, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow, UK
Daniel J. Smith
Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK; Corresponding author at: Institute of Health and Wellbeing, University of Glasgow, Room 111, Public Health, 1 Lilybank Gardens, Glasgow G12 8RZ, UK.
Background: 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. Although suicide results from a complex interaction of multiple social and psychological factors, predisposition to suicidality is at least partly genetic. Methods: Ordinal 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). Outcomes: We 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). Interpretation: These 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. Fund: UKRI 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).
