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

ABSTRACT: 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).

SUBMITTER: Strawbridge RJ

PROVIDER: S-EPMC6442001 | biostudies-literature | 2019 Mar

REPOSITORIES: biostudies-literature

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

Strawbridge Rona J RJ Ward Joey J Ferguson Amy A Graham Nicholas N Shaw Richard J RJ Cullen Breda B Pearsall Robert R Lyall Laura M LM Johnston Keira J A KJA Niedzwiedz Claire L CL Pell Jill P JP Mackay Daniel D Martin Julie Langan JL Lyall Donald M DM Bailey Mark E S MES Smith Daniel J DJ

EBioMedicine 20190208

<h4>Background</h4>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.<h4>Methods</h4>Ordinal genome-wide association study of suicidality in the UK Biobank cohort comparing: 'no suicidality' controls (N = 83,557); 'thoughts t ...[more]

PMID: 30745170

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Project description:While psychotic experiences are core symptoms of mental health disorders like schizophrenia, they are also reported by 5-10% of the population. Both smoking behaviour and genetic risk for psychiatric disorders have been associated with psychotic experiences, but the interplay between these factors remains poorly understood. We tested whether smoking status, maternal smoking around birth, and number of packs smoked/year were associated with lifetime occurrence of three psychotic experiences phenotypes: delusions (n = 2067), hallucinations (n = 6689), and any psychotic experience (delusions or hallucinations; n = 7803) in 157,366 UK Biobank participants. We next calculated polygenic risk scores for schizophrenia (PRSSCZ), bipolar disorder (PRSBP), major depression (PRSDEP) and attention deficit hyperactivity disorder (PRSADHD) in 144,818 UK Biobank participants of European ancestry to assess whether association between smoking and psychotic experiences was attenuated after adjustment of diagnosis of psychiatric disorders and the PRSs. Finally, we investigated whether smoking exacerbates the effects of genetic predisposition on the psychotic phenotypes in gene-environment interaction models. Smoking status, maternal smoking, and number of packs smoked/year were associated with psychotic experiences (p < 1.77 × 10-5). Except for packs smoked/year, effects were attenuated but remained significant after adjustment for diagnosis of psychiatric disorders and PRSs (p < 1.99 × 10-3). Gene-environment interaction models showed the effects of PRSDEP and PRSADHD (but not PRSSCZ or PRSBP) on delusions (but not hallucinations) were significantly greater in current smokers compared to never smokers (p < 0.002). There were no significant gene-environment interactions for maternal smoking nor for number of packs smoked/year. Our results suggest that both genetic risk of psychiatric disorders and smoking status may have independent and synergistic effects on specific types of psychotic experiences.

Project description:OBJECTIVE:More than 90% of people who attempt suicide have a psychiatric diagnosis; however, twin and family studies suggest that the genetic etiology of suicide attempt is partially distinct from that of the psychiatric disorders themselves. The authors present the largest genome-wide association study (GWAS) on suicide attempt, using cohorts of individuals with major depressive disorder, bipolar disorder, and schizophrenia from the Psychiatric Genomics Consortium. METHODS:The samples comprised 1,622 suicide attempters and 8,786 nonattempters with major depressive disorder; 3,264 attempters and 5,500 nonattempters with bipolar disorder; and 1,683 attempters and 2,946 nonattempters with schizophrenia. A GWAS on suicide attempt was performed by comparing attempters to nonattempters with each disorder, followed by a meta-analysis across disorders. Polygenic risk scoring was used to investigate the genetic relationship between suicide attempt and the psychiatric disorders. RESULTS:Three genome-wide significant loci for suicide attempt were found: one associated with suicide attempt in major depressive disorder, one associated with suicide attempt in bipolar disorder, and one in the meta-analysis of suicide attempt in mood disorders. These associations were not replicated in independent mood disorder cohorts from the UK Biobank and iPSYCH. No significant associations were found in the meta-analysis of all three disorders. Polygenic risk scores for major depression were significantly associated with suicide attempt in major depressive disorder (R2=0.25%), bipolar disorder (R2=0.24%), and schizophrenia (R2=0.40%). CONCLUSIONS:This study provides new information on genetic associations and demonstrates that genetic liability for major depression increases risk for suicide attempt across psychiatric disorders. Further collaborative efforts to increase sample size may help to robustly identify genetic associations and provide biological insights into the etiology of suicide attempt.

Project description:BackgroundPsychiatric morbidities have been associated with a risk of severe infections through compromised immunity, health behaviours, or both. However, data are scarce on the association between multiple types of pre-pandemic psychiatric disorders and COVID-19. We aimed to assess the association between pre-pandemic psychiatric disorders and the subsequent risk of COVID-19 using UK Biobank.MethodsFor this cohort analysis, we included participants from UK Biobank who were registered in England and excluded individuals who died before Jan 31, 2020, (the start of the COVID-19 outbreak in the UK) or had withdrawn from UK Biobank. Participants diagnosed with a psychiatric disorder before Jan 31 were included in the group of individuals with pre-pandemic psychiatric disorders, whereas participants without a diagnosis before the outbreak were included in the group of individuals without pre-pandemic psychiatric disorders. We used the Public Health England dataset, UK Biobank hospital data, and death registers to collect data on COVID-19 cases. To examine the relationship between pre-pandemic psychiatric disorders and susceptibility to COVID-19, we used logistic regression models to estimate odds ratios (ORs), controlling for multiple confounders and somatic comorbidities. Key outcomes were all COVID-19, COVID-19 specifically diagnosed in inpatient care, and COVID-19-related deaths. ORs were also estimated separately for each psychiatric disorder and on the basis of the number of pre-pandemic psychiatric disorders. As a positive disease control, we repeated analyses for hospitalisation for other infections.FindingsWe included 421 014 UK Biobank participants in our study and assessed their COVID-19 status between Jan 31 and July 26, 2020. 50 809 participants were diagnosed with psychiatric disorders before the outbreak, while 370 205 participants had no psychiatric disorders. The mean age at outbreak was 67·80 years (SD 8·12). We observed an elevated risk of COVID-19 among individuals with pre-pandemic psychiatric disorders compared with that of individuals without such conditions. The fully adjusted ORs were 1·44 (95% CI 1·28-1·62) for All COVID-19 cases, 1·55 (1·34-1·78) for Inpatient COVID-19 cases, and 2·03 (1·59-2·59) for COVID-19-related deaths. We observed excess risk, defined as risk that increased with the number of pre-pandemic psychiatric disorders, across all diagnostic categories of pre-pandemic psychiatric disorders. We also observed an association between psychiatric disorders and elevated risk of hospitalisation due to other infections (OR 1·74, 95% CI 1·58-1·93).InterpretationOur findings suggest that pre-existing psychiatric disorders are associated with an increased risk of COVID-19. These findings underscore the need for surveillance of and care for populations with pre-existing psychiatric disorders during the COVID-19 pandemic.FundingNational Natural Science Foundation of China.

Dataset Information

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

Publications

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

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