scholarly journals Studying individual risk factors for self-harm in the UK Biobank: A polygenic scoring and Mendelian randomisation study

PLoS Medicine ◽  
2020 ◽  
Vol 17 (6) ◽  
pp. e1003137 ◽  
Author(s):  
Kai Xiang Lim ◽  
Frühling Rijsdijk ◽  
Saskia P. Hagenaars ◽  
Adam Socrates ◽  
Shing Wan Choi ◽  
...  
2019 ◽  
Author(s):  
Kai Xiang Lim ◽  
Frühling Rijsdijk ◽  
Saskia P. Hagenaars ◽  
Adam Socrates ◽  
Shing Wan Choi ◽  
...  

AbstractBackgroundMultiple 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.MethodsUsing 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.OutcomesSelf-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.InterpretationAmong 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.FundingLim 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.Research in ContextEvidence before this studyA search was conducted on PubMed for literature from inception until 1st May 2019 using terms related to suicidal self-harm (SSH) and non-suicidal self-harm (NSSH), as well as polygenic risk scores (PRS), (“self-harm”[All Fields] OR “self-injurious”[All Fields] OR “self-mutilation”[All Fields] OR “suicide”[All Fields]) AND (“polygenic”[All Fields] OR “multifactorial inheritance”[All Fields]). Similar search was done for Mendelian Randomisation (MR), replacing “multifactorial inheritance” and “polygenic” with “Mendelian Randomisation/Randomization”. Evidence was included only if the study had used PRS or MR method to predict self-harm phenotypes using risk factors of self-harm. Ten papers for PRS and no paper for MR were identified.There were mixed results for PRS studies. PRS for MDD predicted SSH in two studies but not in another two studies. PRS for depressive symptoms predicted SSH but not NSSH. PRS for schizophrenia predicted SSH in one but not in another two studies. PRS for bipolar disorder predicted SSH in one study but did not predict SSH nor NSSH in another two studies.Added value of this studyBy using a large population-based sample, we systematically studied individual vulnerabilities and traits that can potentially lead to self-harm, including mental health vulnerabilities, substance use phenotypes, cognitive traits, personality traits and physical traits, summing up to 24 PRS as genetic proxies for 24 risk factors. We conducted MR to strengthen causal inference. We further distinguished non-suicidal self-harm (NSSH) and suicidal self-harm (SSH).Apart from PRS for schizophrenia, MDD and bipolar disorder, novel PRS were also identified to be associated with self-harm, which are PRS for attention-deficit hyperactivity disorder (ADHD), cannabis use and alcohol dependence. A larger sample size allowed us to confirm positive findings from the previously mixed literature regarding the associations between PRS for MDD, bipolar disorder, and schizophrenia with self-harm. Multivariate analyses and MR analyses strengthened the evidence implicating MDD, ADHD and schizophrenia as plausible causal risk factors for self-harm.Implications of all the available evidenceAmong the 24 risk factors considered, plausible causal risk factors for self-harm were identified among psychiatric conditions. Using PRS and MR methods and a number of complementary analyses provided higher confidence to infer causality and nuanced insights into the aetiology of self-harm. From a clinical perspective, detection and treatment of core symptoms of these conditions, such as psychotic or impulsivity symptoms, may prevent individuals from self-harming.


2017 ◽  
Vol 18 (6) ◽  
pp. 296-300 ◽  
Author(s):  
Lasantha Ratnayake ◽  
Amy Harris ◽  
Doreen Ko ◽  
Linda Hawtin

Background: Incidence of carbapenemase-producing enterobacteriaceae (CPE) in the UK is increasing. In 2013, Public Health England (PHE) published a toolkit to control spread of CPE within healthcare settings. Aim: To assess compliance to hospital CPE policy (adapted from PHE) in the identification, isolation and screening of suspected CPE patients. Methods: Admission booklets of 150 patients were evaluated to see whether the relevant section had been completed to identify high-risk CPE patients. Where necessary, patients were interviewed or their GPs were contacted to assess their CPE risk. Additionally, 28 patients screened for CPE were audited to assess compliance to screening and isolation. Findings: Only 23 patients out of 147 (15.6%) were risk assessed on admission. Risk status of 27 (18.4%) patients could not be assessed due to lack of data. Fifteen patients out of 28 (54%) screened for CPE were identified and isolated on admission. Ten out of 19 patients (53%) had three screens 48 h apart. Discussion: This audit highlights difficulties in screening based on individual risk factors as the majority of patients were not screened on admission and documentation on isolation and screening was poor. More needs to be done to raise awareness of the requirements for routine assessment, isolation and screening.


1997 ◽  
Vol 70 (4) ◽  
pp. 387-393 ◽  
Author(s):  
Jan Scott ◽  
Richard House ◽  
Martin Yates ◽  
Jill Harrington

Crisis ◽  
2000 ◽  
Vol 21 (2) ◽  
pp. 80-89 ◽  
Author(s):  
Maila Upanne

This study monitored the evolution of psychologists' (n = 31) conceptions of suicide prevention over the 9-year course of the National Suicide Prevention Project in Finland and assessed the feasibility of the theoretical model for analyzing suicide prevention developed in earlier studies [ Upanne, 1999a , b ]. The study was formulated as a retrospective self-assessment where participants compared their earlier descriptions of suicide prevention with their current views. The changes in conceptions were analyzed and interpreted using both the model and the explanations given by the subjects themselves. The analysis proved the model to be a useful framework for revealing the essential features of prevention. The results showed that the freely-formulated ideas on prevention were more comprehensive than those evolved in practical work. Compared to the earlier findings, the conceptions among the group had shifted toward emphasizing a curative approach and the significance of individual risk factors. In particular, greater priority was focused on the acute suicide risk phase as a preventive target. Nonetheless, the overall structure of prevention ideology remained comprehensive and multifactorial, stressing multistage influencing. Promotive aims (protective factors) also remained part of the prevention paradigm. Practical working experiences enhanced the psychologists' sense of the difficulties of suicide prevention as well as their criticism and feeling of powerlessness.


Author(s):  
Meizi Wang ◽  
Jianhua Ying ◽  
Ukadike Chris Ugbolue ◽  
Duncan S. Buchan ◽  
Yaodong Gu ◽  
...  

(1) Background: Scotland has one of the highest rates of obesity in the Western World, it is well established that poor weight profiles, and particularly abdominal obesity, is strongly associated with Type II diabetes and cardiovascular diseases. Whether these associations are apparent in ethnic population groups in Scotland is unclear. The purpose of this study was to examine the associations between different measures of fatness with clustered cardio metabolic risk factors between Scottish South Asian adolescents and Scottish Caucasian adolescents; (2) Methods: A sample of 208 Caucasian adolescents and 52 South Asian adolescents participated in this study. Stature, waist circumference, body mass index, blood pressure, physical activity, and cardiovascular disease (CVD) risk were measured; (3) Results: Significant, partial correlations in the South Asian cohort between body mass index (BMI) and individual risk factors were generally moderate. However, correlations between Waist circumference (WC) and individual risk factors were significant and strong. In the Caucasian cohort, a significant yet weak correlation between WC and total cholesterol (TG) was noted although no other associations were evident for either WC or BMI. Multiple regression analysis revealed that both BMI and WC were positively associated with CCR (p < 0.01) in the South Asian group and with the additional adjustment of either WC or BMI, the independent associations with clustered cardio-metabolic risk (CCR) remained significant (p < 0.005); (4) Conclusions: No positive relationships were found between BMI, WC, and CCR in the Caucasian group. Strong and significant associations between measures of fatness and metabolic risk were evident in Scottish South Asian adolescents.


SLEEP ◽  
2021 ◽  
Vol 44 (Supplement_2) ◽  
pp. A273-A273
Author(s):  
Xi Zheng ◽  
Ma Cherrysse Ulsa ◽  
Peng Li ◽  
Lei Gao ◽  
Kun Hu

Abstract Introduction While there is emerging evidence for acute sleep disruption in the aftermath of coronavirus disease 2019 (COVID-19), it is unknown whether sleep traits contribute to mortality risk. In this study, we tested whether earlier-life sleep duration, chronotype, insomnia, napping or sleep apnea were associated with increased 30-day COVID-19 mortality. Methods We included 34,711 participants from the UK Biobank, who presented for COVID-19 testing between March and October 2020 (mean age at diagnosis: 69.4±8.3; range 50.2–84.6). Self-reported sleep duration (less than 6h/6-9h/more than 9h), chronotype (“morning”/”intermediate”/”evening”), daytime dozing (often/rarely), insomnia (often/rarely), napping (often/rarely) and presence of sleep apnea (ICD-10 or self-report) were obtained between 2006 and 2010. Multivariate logistic regression models were used to adjust for age, sex, education, socioeconomic status, and relevant risk factors (BMI, hypertension, diabetes, respiratory diseases, smoking, and alcohol). Results The mean time between sleep measures and COVID-19 testing was 11.6±0.9 years. Overall, 5,066 (14.6%) were positive. In those who were positive, 355 (7.0%) died within 30 days (median = 8) after diagnosis. Long sleepers (&gt;9h vs. 6-9h) [20/103 (19.4%) vs. 300/4,573 (6.6%); OR 2.09, 95% 1.19–3.64, p=0.009), often daytime dozers (OR 1.68, 95% 1.04–2.72, p=0.03), and nappers (OR 1.52, 95% 1.04–2.23, p=0.03) were at greater odds of mortality. Prior diagnosis of sleep apnea also saw a two-fold increased odds (OR 2.07, 95% CI: 1.25–3.44 p=0.005). No associations were seen for short sleepers, chronotype or insomnia with COVID-19 mortality. Conclusion Data across all current waves of infection show that prior sleep traits/disturbances, in particular long sleep duration, daytime dozing, napping and sleep apnea, are associated with increased 30-day mortality after COVID-19, independent of health-related risk factors. While sleep health traits may reflect unmeasured poor health, further work is warranted to examine the exact underlying mechanisms, and to test whether sleep health optimization offers resilience to severe illness from COVID-19. Support (if any) NIH [T32GM007592 and R03AG067985 to L.G. RF1AG059867, RF1AG064312, to K.H.], the BrightFocus Foundation A2020886S to P.L. and the Foundation of Anesthesia Education and Research MRTG-02-15-2020 to L.G.


BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Jessica Gong ◽  
Katie Harris ◽  
Sanne A. E. Peters ◽  
Mark Woodward

Abstract Background Sex differences in major cardiovascular risk factors for incident (fatal or non-fatal) all-cause dementia were assessed in the UK Biobank. The effects of these risk factors on all-cause dementia were explored by age and socioeconomic status (SES). Methods Cox proportional hazards models were used to estimate hazard ratios (HRs) and women-to-men ratio of HRs (RHR) with 95% confidence intervals (CIs) for systolic blood pressure (SBP) and diastolic blood pressure (DBP), smoking, diabetes, adiposity, stroke, SES and lipids with dementia. Poisson regression was used to estimate the sex-specific incidence rate of dementia for these risk factors. Results 502,226 individuals in midlife (54.4% women, mean age 56.5 years) with no prevalent dementia were included in the analyses. Over 11.8 years (median), 4068 participants (45.9% women) developed dementia. The crude incidence rates were 5.88 [95% CI 5.62–6.16] for women and 8.42 [8.07–8.78] for men, per 10,000 person-years. Sex was associated with the risk of dementia, where the risk was lower in women than men (HR = 0.83 [0.77–0.89]). Current smoking, diabetes, high adiposity, prior stroke and low SES were associated with a greater risk of dementia, similarly in women and men. The relationship between blood pressure (BP) and dementia was U-shaped in men but had a dose-response relationship in women: the HR for SBP per 20 mmHg was 1.08 [1.02–1.13] in women and 0.98 [0.93–1.03] in men. This sex difference was not affected by the use of antihypertensive medication at baseline. The sex difference in the effect of raised BP was consistent for dementia subtypes (vascular dementia and Alzheimer’s disease). Conclusions Several mid-life cardiovascular risk factors were associated with dementia similarly in women and men, but not raised BP. Future bespoke BP-lowering trials are necessary to understand its role in restricting cognitive decline and to clarify any sex difference.


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