scholarly journals Medical and neurobehavioural phenotypes in carriers of X-linked ichthyosis-associated genetic deletions in the UK Biobank

2020 ◽  
Vol 57 (10) ◽  
pp. 692-698 ◽  
Author(s):  
Lucija Brcic ◽  
Jack FG Underwood ◽  
Kimberley M Kendall ◽  
Xavier Caseras ◽  
George Kirov ◽  
...  
Keyword(s):  
Fluid Intelligence ◽  
Young Patients ◽  
Small Samples ◽  
Adult Males ◽  
Uk Biobank ◽  
Cohen’S D ◽  
Increased Risk ◽  
The Uk ◽  
Cohen's D ◽  
Mental Health Questionnaire

BackgroundX-linked ichthyosis (XLI) is an uncommon dermatological condition resulting from a deficiency of the enzyme steroid sulfatase (STS), often caused by X-linked deletions spanning STS. Some medical comorbidities have been identified in XLI cases, but small samples of relatively young patients has limited this. STS is highly expressed in subcortical brain structures, and males with XLI and female deletion carriers appear at increased risk of developmental/mood disorders and associated traits; the neurocognitive basis of these findings has not been examined.MethodsUsing the UK Biobank resource, comprising participants aged 40–69 years recruited from the general UK population, we compared multiple medical/neurobehavioural phenotypes in males (n=86) and females (n=312) carrying genetic deletions spanning STS (0.8–2.5 Mb) (cases) to male (n=190 577) and female (n=227 862) non-carrier controls.ResultsWe identified an elevated rate of atrial fibrillation/flutter in male deletion carriers (10.5% vs 2.7% in male controls, Benjamini-Hochberg corrected p=0.009), and increased rates of mental distress (p=0.003), irritability (p<0.001) and depressive-anxiety traits (p<0.05) in male deletion carriers relative to male controls completing the Mental Health Questionnaire. While academic attainment was unaffected, male and female deletion carriers exhibited impaired performance on the Fluid Intelligence Test (Cohen’s d≤0.05, corrected p<0.1). Neuroanatomical analysis in female deletion carriers indicated reduced right putamen and left nucleus accumbens volumes (Cohen’s d≤0.26, corrected p<0.1).ConclusionAdult males with XLI disease-causing deletions are apparently at increased risk of cardiac arrhythmias and self-reported mood problems; altered basal ganglia structure may underlie altered function and XLI-associated psychiatric/behavioural phenotypes. These results provide information for genetic counselling of deletion-carrying individuals and reinforce the need for multidisciplinary medical care.

scholarly journals Socioeconomic Inequalities and Ethnicity Are Associated with a Positive COVID-19 Test among Cancer Patients in the UK Biobank Cohort

Cancers ◽  
2021 ◽  
Vol 13 (7) ◽  
pp. 1514
Author(s):  
Shing Fung Lee ◽  
Maja Nikšić ◽  
Bernard Rachet ◽  
Maria-Jose Sanchez ◽  
Miguel Angel Luque-Fernandez
Keyword(s):  
Cancer Patients ◽  
Socioeconomic Inequalities ◽  
Uk Biobank ◽  
Incident Cancer ◽  
Increased Risk ◽  
Exposure Variable ◽  
Independent Risk Factors ◽  
The Uk ◽  
Deprived Areas

We explored the role of socioeconomic inequalities in COVID-19 incidence among cancer patients during the first wave of the pandemic. We conducted a case-control study within the UK Biobank cohort linked to the COVID-19 tests results available from 16 March 2020 until 23 August 2020. The main exposure variable was socioeconomic status, assessed using the Townsend Deprivation Index. Among 18,917 participants with an incident malignancy in the UK Biobank cohort, 89 tested positive for COVID-19. The overall COVID-19 incidence was 4.7 cases per 1000 incident cancer patients (95%CI 3.8–5.8). Compared with the least deprived cancer patients, those living in the most deprived areas had an almost three times higher risk of testing positive (RR 2.6, 95%CI 1.1–5.8). Other independent risk factors were ethnic minority background, obesity, unemployment, smoking, and being diagnosed with a haematological cancer for less than five years. A consistent pattern of socioeconomic inequalities in COVID-19 among incident cancer patients in the UK highlights the need to prioritise the cancer patients living in the most deprived areas in vaccination planning. This socio-demographic profiling of vulnerable cancer patients at increased risk of infection can inform prevention strategies and policy improvements for the coming pandemic waves.

scholarly journals New technical advances in swivel walkers

2003 ◽  
Vol 27 (2) ◽  
pp. 132-138 ◽  
Author(s):  
J. Stallard ◽  
B. Lomas ◽  
P. Woollam ◽  
I. R. Farmer ◽  
N. Jones ◽  
...  
Keyword(s):  
Spina Bifida ◽  
Muscular Atrophy ◽  
Young Patients ◽  
Suitable Alternative ◽  
Detail Design ◽  
Increased Risk ◽  
Technical Advances ◽  
Disabled Patients ◽  
Manual Handling ◽  
The Uk

Swivel walkers were commonly prescribed for children with complete thoracic lesion myelomeningocele in the 1970s and 80s, when the incidence of spina bifida in the UK was of the order of 3 per 100,000 live births. The advent of reciprocal walking orthoses provided a more suitable alternative for those with good upper limb and trunk function, and swivel walkers were then used primarily for very young or more severely disabled patients. Prenatal screening has dramatically reduced the incidence of spina bifida in the UK and subsequently swivel walkers have been used in a wider range of pathology, including spinal muscular atrophy, multiple sclerosis, muscular dystrophy and other neurological conditions that lead to lower limb dysfunction. The detail design of these devices has been adapted to accommodate the specific problems encountered in these conditions. In particular the designs have been updated to: enable very young patients to be more readily fitted at the age of 1 year; allow the walking mechanisms to be conveniently adjusted for easier ambulation when weakness or lack of confidence inhibits performance; permit simple adjustment to a standing frame mode to enhance stability in situations of increased risk; promote manual handling practice that is compatible with the National Health Service (NHS) policy of compliance with relevant regulations. To underpin appropriate prescription and safe supply the NHS Procurement Agency have encouraged the development of a common course for all types of swivel walker.

scholarly journals Polygenic risk for schizophrenia and season of birth within the UK Biobank cohort

2018 ◽  
Vol 49 (15) ◽  
pp. 2499-2504 ◽  
Author(s):  
Valentina Escott-Price ◽  
Daniel J. Smith ◽  
Kimberley Kendall ◽  
Joey Ward ◽  
George Kirov ◽  
...  
Keyword(s):  
Environmental Exposure ◽  
Copy Number Variants ◽  
Season Of Birth ◽  
Uk Biobank ◽  
Month Of Birth ◽  
Risk Alleles ◽  
Gene Environment ◽  
Increased Risk ◽  
The Uk ◽  
Pathogenic Process

AbstractBackgroundThere is strong evidence that people born in winter and in spring have a small increased risk of schizophrenia. As this ‘season of birth’ effect underpins some of the most influential hypotheses concerning potentially modifiable risk exposures, it is important to exclude other possible explanations for the phenomenon.MethodsHere we sought to determine whether the season of birth effect reflects gene-environment confounding rather than a pathogenic process indexing environmental exposure. We directly measured, in 136 538 participants from the UK Biobank (UKBB), the burdens of common schizophrenia risk alleles and of copy number variants known to increase the risk for the disorder, and tested whether these were correlated with a season of birth.ResultsNeither genetic measure was associated with season or month of birth within the UKBB sample.ConclusionsAs our study was highly powered to detect small effects, we conclude that the season of birth effect in schizophrenia reflects a true pathogenic effect of environmental exposure.

scholarly journals Associations of cigarette smoking with gray and white matter in the UK Biobank

2019 ◽  
Author(s):  
Joshua Gray ◽  
Matthew Thompson ◽  
Chelsie Benca-Bachman ◽  
Max Michael Owens ◽  
Mikela Murphy ◽  
...  
Keyword(s):  
White Matter ◽  
Cigarette Smoking ◽  
Gray Matter ◽  
Brain Structure ◽  
Mean Diffusivity ◽  
Medial Lemniscus ◽  
Uk Biobank ◽  
Matter Volume ◽  
Increased Risk ◽  
The Uk

Chronic cigarette smoking is associated with increased risk for myriad health consequences including cognitive decline and dementia, but research on the link between smoking and brain structure is nascent. We assessed the relationship of cigarette smoking (ever smoked, cigarettes per day, and duration) with gray and white matter using the UK Biobank cohort (gray matter N = 19,615; white matter N = 17,760), adjusting for numerous demographic and health confounders. Ever smoked and duration were associated with smaller total gray matter volume. Ever smoked was associated with reduced volume of the right VIIIa cerebellum, as well as elevated white matter hyperintensity volumes. Smoking duration was associated with reduced total white matter volume. With regard to specific tracts, ever smoked was associated with reduced fractional anisotropy in the left cingulate gyrus part of the cingulum, left posterior thalamic radiation, and bilateral superior thalamic radiation and increased mean diffusivity in the middle cerebellar peduncle, right medial lemniscus, bilateral posterior thalamic radiation, and bilateral superior thalamic radiation. Overall, we found significant associations of cigarette exposure with global measures of gray and white matter. Furthermore, we found select associations of ever smoked, but not cigarettes per day or duration, with specific gray and white matter regions. These findings inform our understanding of the connections between smoking and variation in brain structure and clarify potential mechanisms of risk for common neurological sequelae.

scholarly journals Diabetes, glycated haemoglobin and the risk of myocardial infarction in women and men: a prospective cohort study of the UK Biobank

2020 ◽  
Author(s):  
Marit de Jong ◽  
Mark Woodward ◽  
Sanne A.E Peters
Keyword(s):  
Myocardial Infarction ◽  
Sex Differences ◽  
Glycated Haemoglobin ◽  
Incidence Rates ◽  
Undiagnosed Diabetes ◽  
Uk Biobank ◽  
Diabetes Status ◽  
Increased Risk ◽  
The Uk ◽  
Diagnosed Diabetes

<b>Objective:</b> Diabetes has shown to be a stronger risk factor for myocardial infarction (MI) in women than men. Whether sex differences exist across the glycaemic spectrum is unknown. We investigated sex differences in the associations of diabetes status and glycated haemoglobin (HbA1c) with the risk of MI. <br> <b>Research Design and Methods:</b> Data were used from 471,399 (56% women) individuals without cardiovascular disease (CVD) included in the UK Biobank. Sex-specific incidence rates were calculated by diabetes status and across levels of HbA1c, using Poisson regression. Cox proportional hazards analyses estimated sex-specific hazard ratios (HR) and women-to-men ratios by diabetes status and HbA1c for MI during a mean follow-up of 9 years. <br> <b>Results:</b> Women had lower incidence rates of MI than men, regardless of diabetes status or HbA1c level. Compared with individuals without diabetes, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes were associated with increased risk of MI in both sexes. Previously diagnosed diabetes was more strongly associated with MI in women (HR 2∙33 [95%CI 1∙96;2∙78]) than men (1∙81 [1∙63;2∙02]), with a women-to-men ratio of HRs of 1∙29 (1∙05;1∙58). Each 1% higher HbA1c, independent of diabetes status, was associated with an 18% greater risk of MI in both women and men.<br> <b>Conclusions:</b> Although the incidence of MI was higher in men than women, the presence of diabetes is associated with a greater excess relative risk of MI in women. However, each 1% higher HbA1c was associated with an 18% greater risk of MI in both women and men.<br> <br>

scholarly journals Diabetes, glycated haemoglobin and the risk of myocardial infarction in women and men: a prospective cohort study of the UK Biobank

2020 ◽  
Author(s):  
Marit de Jong ◽  
Mark Woodward ◽  
Sanne A.E Peters
Keyword(s):  
Myocardial Infarction ◽  
Sex Differences ◽  
Glycated Haemoglobin ◽  
Incidence Rates ◽  
Undiagnosed Diabetes ◽  
Uk Biobank ◽  
Diabetes Status ◽  
Increased Risk ◽  
The Uk ◽  
Diagnosed Diabetes

<b>Objective:</b> Diabetes has shown to be a stronger risk factor for myocardial infarction (MI) in women than men. Whether sex differences exist across the glycaemic spectrum is unknown. We investigated sex differences in the associations of diabetes status and glycated haemoglobin (HbA1c) with the risk of MI. <br> <b>Research Design and Methods:</b> Data were used from 471,399 (56% women) individuals without cardiovascular disease (CVD) included in the UK Biobank. Sex-specific incidence rates were calculated by diabetes status and across levels of HbA1c, using Poisson regression. Cox proportional hazards analyses estimated sex-specific hazard ratios (HR) and women-to-men ratios by diabetes status and HbA1c for MI during a mean follow-up of 9 years. <br> <b>Results:</b> Women had lower incidence rates of MI than men, regardless of diabetes status or HbA1c level. Compared with individuals without diabetes, prediabetes, undiagnosed diabetes, and previously diagnosed diabetes were associated with increased risk of MI in both sexes. Previously diagnosed diabetes was more strongly associated with MI in women (HR 2∙33 [95%CI 1∙96;2∙78]) than men (1∙81 [1∙63;2∙02]), with a women-to-men ratio of HRs of 1∙29 (1∙05;1∙58). Each 1% higher HbA1c, independent of diabetes status, was associated with an 18% greater risk of MI in both women and men.<br> <b>Conclusions:</b> Although the incidence of MI was higher in men than women, the presence of diabetes is associated with a greater excess relative risk of MI in women. However, each 1% higher HbA1c was associated with an 18% greater risk of MI in both women and men.<br> <br>

Understanding Language Features in Loneliness Forum Posts that Elicit Comments (Preprint)

2021 ◽  
Author(s):  
Anietie Andy
Keyword(s):  
Language Processing ◽  
Latent Dirichlet Allocation ◽  
Well Being ◽  
Time Of Day ◽  
Online Forums ◽  
Cohen’S D ◽  
Increased Risk ◽  
Social Media Platforms ◽  
Cohen's D ◽  
To Receive

BACKGROUND Loneliness is a threat to the well-being of individuals and in older adults is associated with increased risk of early mortality. Studies have shown that some individuals seek support around loneliness on online forums/social media platforms. A common challenge in online forums is that some posts do not receive comments. In some non-health related forums, posts not receiving comments may not be a serious concern, however, in an online health forum such as those focused on discussions around loneliness, posts not receiving comments could translate to individuals seeking support around loneliness not receiving adequate support. OBJECTIVE The aim of this work is to analyze posts published on an active online forum focused on discussions around loneliness (loneliness forum) to determine the language features associated with posts that elicit comments from members of the forum. METHODS For the analysis in this work, 15,012 posts published on an online loneliness forum by 9,956 users were analyzed. Of these posts, 6,450 received five or more comments, 13,221 received one or more comments, and 1,791 received no comments. Using the natural language processing method, latent dirichlet allocation (LDA) and a psycholinguistic dictionary, Linguistics Inquiry and Word Count (LIWC), the language features expressed in posts that elicit comments from members of the forum were determined. RESULTS The findings from this work show that posts related to topics themes on relationships (Cohen’s D = 0.319) and the use of negation words (Cohen’s D = 0.149) tend to receive one or more comments. Also, posts associated with LIWC categories on first person singular pronouns (Cohen’s D = 0.264) tend to elicit one or more comments. Posts on topic themes related to spending time around holidays/birthdays/year/time of day or week (Cohen’s D = 0.79) and affection relative to relationships (Cohen’s D = 0.102) tend to receive five or more comments. CONCLUSIONS This work identifies language features expressed in loneliness forum posts that elicit comments. The findings from this work can provide members of online loneliness forums tips on how to write posts that potentially elicit comments from members of the forum.

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

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.

Abstract P147: Genome Wide Assessment of Shared Genetic Architecture Between Rheumatoid Arthritis and Cardiovascular Diseases Using the UK Biobank Data

Circulation ◽  
2020 ◽  
Vol 141 (Suppl_1) ◽  
Author(s):  
Yanjun Guo ◽  
Wonil Chung ◽  
Zhilei Shan ◽  
Liming Liang
Keyword(s):  
Cardiovascular Diseases ◽  
Genetic Correlation ◽  
Multiple Testing ◽  
Mendelian Randomization ◽  
Meta Analysis ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk ◽  
Cardiovascular Traits ◽  
Shared Genetic

Background: Patients with RA have a 2-10 folds increased risk of cardiovascular diseases (CVD) and CVD accounts for almost 50% of the excess mortality in patients with RA when compared with general population, but the mechanisms underlying such associations are largely unknown. Methods: We examined the genetic correlation, causality, and shared genetic variants between RA (Ncase=6,756, Ncontrol=452,476) and CVD (Ncase=44,246, Ncontrol=414,986) using LD Score regression (LDSC), generalized summary-data-based Mendelian Randomization (GSMR), and cross-trait meta-analysis in the UK Biobank Data. Results: In the present study, RA was significantly genetically correlated with MI, angina, CHD, and CVD after correcting for multiple testing (Rg ranges from 0.40 to 0.43, P<0.05/5). Interestingly, when stratified by frequent usage of aspirin and paracetamol, we observed increased genetic correlation between RA and CVD for participants without aspirin usage ( Rg increased to 0.54 [95%CI: 0.54, 0.78] for angina; P value=6.69х10 -6 ), and for participants with usage of paracetamol ( Rg increased to 0.75 [95%CI: 0.20, 1.29] for MI; P value=8.90х10 -3 ). Cross-trait meta-analysis identified 9 independent loci that were shared between RA and at least one of the genetically correlated CVD traits including PTPN22 at chr1p13.2 , BCL2L11 at chr2q13 , and CCR3 at chr3p21.31 ( P single trait <1х10 -3 and P meta <5х10 -8 ) highlighting potential shared etiology between them which include accelerating atherosclerosis and upregulating oxidative stress and vascular permeability. Finally, Mendelian randomization analyses observed inconsistent instrumental effects and were unable to conclude the causality and directionality between RA and CVD. Conclusion: Our results supported positive genetic correlation between RA and multiple cardiovascular traits, and frequent usage of aspirin and paracetamol may modify their associations, but instrumental analyses were unable to conclude the causality and directionality between them.

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

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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