OP63 Loneliness, living arrangements and emotional support as predictors of suicidality: a 7 year follow-up of the UK biobank cohort

AbstractBackgroundThe association between loneliness and suicide is complex, poorly understood, and there are no prior longitudinal studies. We aimed to investigate the relationship between living alone, loneliness and emotional support as predictors of death by suicide and self-harm.MethodsBetween 2006 and 2010 UK Biobank recruited over 0.5m people aged 37-73. This data was linked to prospective hospital admission and mortality records. Adjusted Cox regression models were used to investigate the relationship between self-reported measures of loneliness, emotional support and living arrangements and death by suicide and self-harm.ResultsFor women, there was no evidence that living arrangements, loneliness or lack of emotional support were associated with death by suicide. However, for men, both living alone (Hazard Ratio (HR) 2.19 95%CI 1.47-3.27) and with non-partners (HR 2.17 95%CI 1.28-3.69) were associated with death by suicide, independently of loneliness, which had a modest relationship with suicide in men (HR 1.45 95%CI 0.99-2.12). Associations between living alone and self-harm were explained by health for women, and by health, loneliness and emotional support for men. In fully adjusted models, loneliness was associated with hospital admissions for self-harm in both women (HR 1.90 95%CI 1.58-2.29) and men (HR 1.75 95%CI 1.41-2.18).ConclusionsFor men -but not for women- living alone or with a non-partner increased the risk of suicide, a finding not explained by loneliness. Loneliness may be more important as a risk factor for self-harm than for suicide, and appears to mitigate against any protective effect of cohabitation.

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Living alone, loneliness and lack of emotional support as predictors of suicide and self-harm: A nine-year follow up of the UK Biobank cohort

Journal of Affective Disorders ◽

10.1016/j.jad.2020.10.026 ◽

2021 ◽

Vol 279 ◽

pp. 316-323

Author(s):

Richard J. Shaw ◽

Breda Cullen ◽

Nicholas Graham ◽

Donald M. Lyall ◽

Daniel Mackay ◽

...

Keyword(s):

Emotional Support ◽

Living Alone ◽

Uk Biobank ◽

Self Harm ◽

The Uk

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Hemochromatosis Mutations, Brain Iron Imaging, and Dementia in the UK Biobank Cohort

Journal of Alzheimer s Disease ◽

10.3233/jad-201080 ◽

2021 ◽

pp. 1-9

Author(s):

Janice L. Atkins ◽

Luke C. Pilling ◽

Christine J. Heales ◽

Sharon Savage ◽

Chia-Ling Kuo ◽

...

Keyword(s):

Iron Reduction ◽

Brain Mri ◽

European Ancestry ◽

Uk Biobank ◽

Brain Iron ◽

Mri Features ◽

Incident Dementia ◽

Hfe Mutations ◽

The Uk

Background: Brain iron deposition occurs in dementia. In European ancestry populations, the HFE p.C282Y variant can cause iron overload and hemochromatosis, mostly in homozygous males. Objective: To estimated p.C282Y associations with brain MRI features plus incident dementia diagnoses during follow-up in a large community cohort. Methods: UK Biobank participants with follow-up hospitalization records (mean 10.5 years). MRI in 206 p.C282Y homozygotes versus 23,349 without variants, including T2 * measures (lower values indicating more iron). Results: European ancestry participants included 2,890 p.C282Y homozygotes. Male p.C282Y homozygotes had lower T2 * measures in areas including the putamen, thalamus, and hippocampus, compared to no HFE mutations. Incident dementia was more common in p.C282Y homozygous men (Hazard Ratio HR = 1.83; 95% CI 1.23 to 2.72, p = 0.003), as was delirium. There were no associations in homozygote women or in heterozygotes. Conclusion: Studies are needed of whether early iron reduction prevents or slows related brain pathologies in male HFE p.C282Y homozygotes.

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Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319508 ◽

2021 ◽

pp. bjophthalmol-2021-319508

Author(s):

Xianwen Shang ◽

Zhuoting Zhu ◽

Yu Huang ◽

Xueli Zhang ◽

Wei Wang ◽

...

Keyword(s):

Heart Disease ◽

Age Related Macular Degeneration ◽

Hospital Inpatient ◽

Uk Biobank ◽

Age Related ◽

Incident Dementia ◽

Increased Risk ◽

The Uk ◽

Systemic Condition

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

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Associations of BMI and Serum Urate with Developing Dementia: A Prospective Cohort Study

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa638 ◽

2020 ◽

Vol 105 (12) ◽

pp. e4688-e4698

Author(s):

Zhi Cao ◽

Chenjie Xu ◽

Hongxi Yang ◽

Shu Li ◽

Fusheng Xu ◽

...

Keyword(s):

Body Mass Index ◽

Cohort Study ◽

Lower Risk ◽

Serum Urate ◽

Healthy Weight ◽

Uk Biobank ◽

Health Records ◽

Increased Risk ◽

The Uk

Abstract Context Recent studies have suggested that a higher body mass index (BMI) and serum urate levels were associated with a lower risk of developing dementia. However, these reverse relationships remain controversial, and whether serum urate and BMI confound each other is not well established. Objectives To investigate the independent associations of BMI and urate, as well as their interaction with the risk of developing dementia. Design and Settings We analyzed a cohort of 502 528 individuals derived from the UK Biobank that included people aged 37–73 years for whom BMI and urate were recorded between 2006 and 2010. Dementia was ascertained at follow-up using electronic health records. Results During a median of 8.1 years of follow-up, a total of 2138 participants developed dementia. People who were underweight had an increased risk of dementia (hazard ratio [HR] = 1.91, 95% confidence interval [CI]: 1.24–2.97) compared with people of a healthy weight. However, the risk of dementia continued to fall as weight increased, as those who were overweight and obese were 19% (HR = 0.81, 95%: 0.73–0.90) and 22% (HR = 0.78, 95% CI: 0.68–0.88) were less likely to develop dementia than people of a healthy weight. People in the highest quintile of urate were also associated with a 25% (HR = 0.75, 95% CI: 0.64–0.87) reduction in the risk of developing dementia compared with those who were in the lowest quintile. There was a significant multiplicative interaction between BMI and urate in relation to dementia (P for interaction = 0.004), and obesity strengthens the protective effect of serum urate on the risk of dementia. Conclusion Both BMI and urate are independent predictors of dementia, and there are inverse monotonic and dose-response associations of BMI and urate with dementia.

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Vaccination history for diphtheria and tetanus is associated with less severe COVID-19

10.1101/2021.06.09.21257809 ◽

2021 ◽

Author(s):

Jennifer Monereo-Sanchez ◽

Jurjen Luykx ◽

Justo Emilio Pinzon-Espinosa ◽

Genevieve Richard ◽

Ehsan Motazadi ◽

...

Keyword(s):

Symptom Severity ◽

Disease Diagnosis ◽

Interindividual Variation ◽

Severe Respiratory Failure ◽

Uk Biobank ◽

Use Of Data ◽

Vaccination History ◽

History Of ◽

The Uk

Background: COVID-19 is characterized by strikingly large, mostly unexplained, interindividual variation in symptom severity. While some individuals remain nearly asymptomatic, others suffer from severe respiratory failure. It has been hypothesized that previous vaccinations for other pathogens, in particular tetanus, may provide protection against severe COVID-19. Methods: We made use of data on COVID-19 testing from 103,049 participants of the UK Biobank (mean age 71.5 years, 54.2% female), coupled to immunization records of the last ten years. Using logistic regression, covarying for age, sex, respiratory disease diagnosis, and socioeconomic status, we tested whether individuals vaccinated for tetanus, diphtheria or pertussis, differed from individuals that had only received other vaccinations on 1) undergoing a COVID-19 test, 2) the outcome of this test, and 3) whether they developed severe COVID-19. Results: We found that individuals with registered diphtheria or tetanus vaccinations were less likely to develop severe COVID-19 than people who had only received other vaccinations (diphtheria OR=0.46, p=3.6x10-4; tetanus OR=0.50, p=5.8x10-4). Discussion: These results indicate that a history of diphtheria or tetanus vaccinations is associated with less severe manifestations of COVID-19. These vaccinations may protect against severe COVID-19 symptoms by stimulating the immune system. We note the correlational nature of these results, yet the possibility that these vaccinations may influence the severity of COVID-19 warrants follow-up investigations.

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Fitness, Fatness, and Mortality in Men and Women From the UK Biobank: Prospective Cohort Study

Journal of the American Heart Association ◽

10.1161/jaha.120.019605 ◽

2021 ◽

Author(s):

Jakob Tarp ◽

Anders Grøntved ◽

Miguel A. Sanchez‐Lastra ◽

Knut Eirik Dalene ◽

Ding Ding ◽

...

Keyword(s):

Body Composition ◽

Cardiorespiratory Fitness ◽

Cox Regression ◽

World Health ◽

Uk Biobank ◽

Men And Women ◽

Increased Risk ◽

All Cause Mortality ◽

The Uk

Background Cardiorespiratory fitness may moderate the association between obesity and all‐cause mortality (ie, the “fat‐but‐fit” hypothesis), but unaddressed sources of bias are a concern. Methods and Results Cardiorespiratory fitness was estimated as watts per kilogram from a submaximal bicycle test in 77 169 men and women from the UK Biobank cohort and combined with World Health Organization standard body mass index categories, yielding 9 unique fitness‐fatness combinations. We also formed fitness‐fatness combinations based on bioimpedance as a direct measure of body composition. All‐cause mortality was ascertained from death registries. Multivariable‐adjusted Cox regression models were used to estimate hazard ratios and 95% CIs. We examined the association between fitness‐fatness combinations and all‐cause mortality in models with progressively more conservative approaches for accounting for reverse causation, misclassification of body composition, and confounding. Over a median follow‐up of 7.7 years, 1731 participants died. In our base model, unfit men and women had higher risk of premature mortality irrespective of levels of adiposity, compared with the normal weight–fit reference. This pattern was attenuated but maintained with more conservative approaches in men, but not in women. In analysis stratified by sex and excluding individuals with prevalent major chronic disease and short follow‐up and using direct measures of body composition, mortality risk was 1.78 (95% CI, 1.17–2.71) times higher in unfit‐obese men but not higher in obese‐fit men (0.94 [95% CI, 0.60–1.48]). In contrast, there was no increased risk in obese‐unfit women (1.09 [95% CI, 0.44–1.05]) as compared with the reference. Conclusions Cardiorespiratory fitness modified the association between obesity and mortality in men, but this pattern appeared susceptible to biases in women.

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Women With Diabetes Are at Increased Relative Risk of Heart Failure Compared to Men: Insights From UK Biobank

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.658726 ◽

2021 ◽

Vol 8 ◽

Author(s):

Sucharitha Chadalavada ◽

Magnus T. Jensen ◽

Nay Aung ◽

Jackie Cooper ◽

Karim Lekadir ◽

...

Keyword(s):

Heart Failure ◽

Cox Regression ◽

Cardiac Risk ◽

Uk Biobank ◽

Contributing Factors ◽

Increased Risk ◽

Study Population ◽

The Uk

Aims: To investigate the effect of diabetes on mortality and incident heart failure (HF) according to sex, in the low risk population of UK Biobank. To evaluate potential contributing factors for any differences seen in HF end-point.Methods: The entire UK Biobank study population were included. Participants that withdrew consent or were diagnosed with diabetes after enrolment were excluded from the study. Univariate and multivariate cox regression models were used to assess endpoints of mortality and incident HF, with median follow-up periods of 9 years and 8 years respectively.Results: A total of 493,167 participants were included, hereof 22,685 with diabetes (4.6%). Two thousand four hundred fifty four died and 1,223 were diagnosed or admitted with HF during the follow up periods of 9 and 8 years respectively. Overall, the mortality and HF risk were almost doubled in those with diabetes compared to those without diabetes (hazard ratio (HR) of 1.9 for both mortality and heart failure) in the UK Biobank population. Women with diabetes (both types) experience a 22% increased risk of HF compared to men (HR of 2.2 (95% CI: 1.9–2.5) vs. 1.8 (1.7–2.0) respectively). Women with type 1 diabetes (T1DM) were associated with 88% increased risk of HF compared to men (HR 4.7 (3.6–6.2) vs. 2.5 (2.0–3.0) respectively), while the risk of HF for type 2 diabetes (T2DM) was 17% higher in women compared to men (2.0 (1.7–2.3) vs. 1.7 (1.6–1.9) respectively). The increased risk of HF in women was independent of confounding factors. The findings were similar in a model with all-cause mortality as a competing risk. This interaction between sex, diabetes and outcome of HF is much more prominent for T1DM (p = 0.0001) than T2DM (p = 0.1).Conclusion: Women with diabetes, particularly those with T1DM, experience a greater increase in risk of heart failure compared to men with diabetes, which cannot be explained by the increased prevalence of cardiac risk factors in this cohort.

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Panomics: New Databases for Advancing Cardiology

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.587768 ◽

2021 ◽

Vol 8 ◽

Author(s):

Dara Vakili ◽

Dina Radenkovic ◽

Shreya Chawla ◽

Deepak L. Bhatt

Keyword(s):

Statistical Power ◽

Biological Variability ◽

Uk Biobank ◽

Inclusion Criteria ◽

Biological Mechanisms ◽

Noisy Signals ◽

Clinical Measurements ◽

The Uk ◽

Study Designs

The multifactorial nature of cardiology makes it challenging to separate noisy signals from confounders and real markers or drivers of disease. Panomics, the combination of various omic methods, provides the deepest insights into the underlying biological mechanisms to develop tools for personalized medicine under a systems biology approach. Questions remain about current findings and anticipated developments of omics. Here, we search for omic databases, investigate the types of data they provide, and give some examples of panomic applications in health care. We identified 104 omic databases, of which 72 met the inclusion criteria: genomic and clinical measurements on a subset of the database population plus one or more omic datasets. Of those, 65 were methylomic, 59 transcriptomic, 41 proteomic, 42 metabolomic, and 22 microbiomic databases. Larger database sample sizes and longer follow-up are often better suited for panomic analyses due to statistical power calculations. They are often more complete, which is important when dealing with large biological variability. Thus, the UK BioBank rises as the most comprehensive panomic resource, at present, but certain study designs may benefit from other databases.

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Identifying genetic variants associated with cerebellar volume in 33,265 individuals from the UK-Biobank

10.1101/2020.11.24.393249 ◽

2020 ◽

Author(s):

Tom Chambers ◽

Valentina Escott-Price ◽

Sophie Legge ◽

Emily Baker ◽

Krish D. Singh ◽

...

Keyword(s):

Association Studies ◽

Brain Structures ◽

Genome Wide Association Studies ◽

Uk Biobank ◽

Protein Coding ◽

Cerebellar Volume ◽

Genome Wide ◽

Subcortical Brain Structures ◽

The Uk

AbstractThere is expanding interest in researching the cerebellum given accumulating evidence of its important contributions to cognitive and emotional functions, in addition to more established sensorimotor roles. While large genome-wide association studies (GWAS) have shed light on the common allele architecture of cortical and subcortical brain structures, the cerebellum remains under investigated. We conducted a meta-GWAS of cerebellar volume in 33,265 UK-Biobank European participants. Results show cerebellar volume to be moderately heritable (h2SNP=50.6%). We identified 33 independent genome-wide associated SNPs with total cerebellar volume, with 6 of these SNPs mapped to protein-coding genes and 5 more shown to alter cerebellar gene expression. We highlight 21 unique candidate genes for follow-up analysis. Cerebellar volume showed significant genetic correlation with brainstem, pallidum and thalamus volumes, but no significant correlations with neuropsychiatric phenotypes. Our results provide important new knowledge of the genetic architecture of cerebellar volume and its relationship with other brain phenotypes.

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