scholarly journals The Association of Age at Diagnosis of Hypertension With Brain Structure and Incident Dementia in the UK Biobank

Hypertension ◽  
2021 ◽  
Author(s):  
Xianwen Shang ◽  
Edward Hill ◽  
Zhuoting Zhu ◽  
Jiahao Liu ◽  
B. Zongyuan Ge ◽  
...  
Keyword(s):  
Gray Matter ◽  
Brain Volume ◽  
Multivariable Analysis ◽  
Brain Magnetic Resonance Imaging ◽  
Hospital Inpatient ◽  
Uk Biobank ◽  
Brain Volumes ◽  
Increased Risk ◽  
The Uk ◽  
Diagnosis Of Hypertension

Little is known about whether the association of hypertension with brain volume and dementia is modified by an individual’s age at their diagnosis of hypertension. Our analysis was based on the UK Biobank with baseline data collected between 2006 and 2010. Brain magnetic resonance imaging was used to measure brain volumes between 2014 and 2019. Dementia was ascertained using hospital inpatient, mortality, and self-reported data until 2021. We randomly selected a control participant for each hypertensive participant stratified by hypertension diagnosis age using propensity score. The cohort comprised 11 399 individuals with hypertension and 11 399 controls for the brain volume analysis and 124 053 individuals with hypertension and 124 053 controls for the dementia analysis. Individuals with hypertension diagnosed at ages <35 (β (95% CI, −10.83 [−19.27 to −2.39] mL), 35 to 44 (−6.82 [−12.18 to −1.46] mL), and 45 to 54 years (−3.77 [−6.91 to −0.64] mL) had smaller total brain volume compared with the corresponding controls in the multivariable analysis. Similarly, hypertension diagnosed in early- and mid-life was independently associated with smaller volumes of gray matter, peripheral cortical gray matter, and white matter. Over a median follow-up of 11.9 years, 4626 cases of incident all-cause dementia were documented. Individuals with hypertension diagnosed at 35 to 44 years of age only (hazard ratio [95% CI]: 1.61 [1.31–1.99]) had a higher risk of all-cause dementia compared with the corresponding controls after adjustment for covariates. Hypertension diagnosed in young adulthood or mid-life, but not late life is associated with smaller brain volumes and an increased risk of dementia.

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.

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.

scholarly journals Genetic predisposition to psychiatric disorders and risk of COVID-19

2021 ◽  
Author(s):  
Wenwen Chen ◽  
Yu Zeng ◽  
Chen Suo ◽  
Huazhen Yang ◽  
Yilong Chen ◽  
...  
Keyword(s):  
Psychiatric Disorder ◽  
Psychiatric Disorders ◽  
Genetic Predisposition ◽  
Genetic Risk ◽  
Substance Misuse ◽  
Hospital Inpatient ◽  
Summary Statistics ◽  
Uk Biobank ◽  
Increased Risk ◽  
The Uk

AbstractBackgroundPre-pandemic psychiatric disorders have been associated with an increased risk of COVID-19. However, the underlying mechanisms remain unknown, e.g. to what extent genetic predisposition to psychiatric disorders contributes to the observed association.MethodsThe analytic sample consisted of white British participants of UK Biobank registered in England, with available genetic data, and alive on Jan 31, 2020 (i.e., the start of the COVID-19 outbreak in the UK) (n=346,554). We assessed individuals’ genetic predisposition to different psychiatric disorders, including substance misuse, depression, anxiety, and psychotic disorder, using polygenic risk score (PRS). Diagnoses of psychiatric disorders were identified through the UK Biobank hospital inpatient data. We performed a GWAS analysis for each psychiatric disorder in a randomly selected half of the study population who were free of COVID-19 (i.e., the base dataset). For the other half (i.e., the target dataset), PRS was calculated for each psychiatric disorder using the discovered genetic variants from the base dataset. We then examined the association between PRS of each psychiatric disorder and risk of COVID-19, or severe COVID-19 (i.e., hospitalization and death), using logistic regression models. The ascertainment of COVID-19 was through the Public Health England dataset, the UK Biobank hospital inpatient data and death registers, updated until July 26, 2020. For validation, we repeated the PRS analyses based on publicly available GWAS summary statistics.Results155,988 participants (including 1,451 COVID-19 cases), with a mean age of 68.50 years at COVID-19 outbreak, were included for PRS analysis. Higher genetic liability forwards psychiatric disorders was associated with increased risk of both any COVID-19 and severe COVID-19, especially genetic risk for substance misuse and depression. The adjusted odds ratios (ORs) for any COVID-19 were 1.15 (95% confidence interval [CI] 1.02-1.31) and 1.26 (1.11-1.42) among individuals with a high genetic risk (above the upper tertile of PRS) for substance misuse and depression, respectively, compared with individuals with a low genetic risk (below the lower tertile). Largely similar ORs were noted for severe COVID-19 and similar albeit slightly lower estimates using PRSs generated from GWAS summary statistics from independent samples.ConclusionIn the UK Biobank, genetic predisposition to psychiatric disorders was associated with an increased risk of COVID-19, including severe course of the disease. These findings suggest the potential role of genetic factors in the observed phenotypic association between psychiatric disorders and COVID-19, underscoring the need of increased medical surveillance of for this vulnerable population during the pandemic.

scholarly journals Evaluating the effect of birth weight on brain volumes and depression: An observational and genetic study using UK Biobank cohort

2020 ◽  
Vol 63 (1) ◽  
Author(s):  
Jing Ye ◽  
Cuiyan Wu ◽  
Xiaomeng Chu ◽  
Yan Wen ◽  
Ping Li ◽  
...  
Keyword(s):  
Birth Weight ◽  
Gray Matter ◽  
Mediation Analysis ◽  
Brain Volume ◽  
Mediation Effect ◽  
Risk Scores ◽  
Uk Biobank ◽  
Phenotypic Data ◽  
Brain Volumes ◽  
Mediation Effects

Abstract Background. Birth weight influences not only brain development, but also mental health outcomes, including depression, but the underlying mechanism is unclear. Methods. The phenotypic data of 12,872–91,009 participants (59.18–63.38% women) from UK Biobank were included to test the associations between the birth weight, depression, and brain volumes through the linear and logistic regression models. As birth weight is highly heritable, the polygenic risk scores (PRSs) of birth weight were calculated from the UK Biobank cohort (154,539 participants, 56.90% women) to estimate the effect of birth weight-related genetic variation on the development of depression and brain volumes. Finally, the mediation analyses of step approach and mediation analysis were used to estimate the role of brain volumes in the association between birth weight and depression. All analyses were conducted sex stratified to assess sex-specific role in the associations. Result. We observed associations between birth weight and depression (odds ratio [OR] = 0.968, 95% confidence interval [CI] = 0.957–0.979, p = 2.29 × 10−6). Positive associations were observed between birth weight and brain volumes, such as gray matter (B = 0.131, p = 3.51 × 10−74) and white matter (B = 0.129, p = 1.67 × 10−74). Depression was also associated with brain volume, such as left thalamus (OR = 0.891, 95% CI = 0.850–0.933, p = 4.46 × 10−5) and right thalamus (OR = 0.884, 95% CI = 0.841–0.928, p = 2.67 × 10−5). Additionally, significant mediation effects of brain volume were found for the associations between birth weight and depression through steps approach and mediation analysis, such as gray matter (B = –0.220, p = 0.020) and right thalamus (B = –0.207, p = 0.014). Conclusions. Our results showed the associations among birth weight, depression, and brain volumes, and the mediation effect of brain volumes also provide evidence for the sex-specific of associations.

scholarly journals Analysis of 200,000 Exome-Sequenced UK Biobank Subjects Implicates Genes Involved in Increased and Decreased Risk of Hypertension

Pulse ◽  
2021 ◽  
pp. 1-13
Author(s):  
David Curtis
Keyword(s):  
Rare Variants ◽  
Soluble Guanylate Cyclase ◽  
Therapeutic Interventions ◽  
Large Contribution ◽  
Protective Effects ◽  
Uk Biobank ◽  
Increased Risk ◽  
Higher Weights ◽  
The Uk ◽  
Diagnosis Of Hypertension

<b><i>Background:</i></b> Previous analyses have identified common variants along with some specific genes and rare variants which are associated with risk of hypertension, but much remains to be discovered. <b><i>Methods and Results:</i></b> Exome-sequenced UK Biobank participants were phenotyped based on having a diagnosis of hypertension or taking anti-hypertensive medication to produce a sample of 66,123 cases and 134,504 controls. Variants with minor allele frequency (MAF) &#x3c;0.01 were subjected to a gene-wise weighted burden analysis, with higher weights assigned to variants which are rarer and/or predicted to have more severe effects. Of 20,384 genes analysed, 2 genes were exome-wide significant, <i>DNMT3A</i> and <i>FES</i>. Also strongly implicated were <i>GUCY1A1</i> and <i>GUCY1B1</i>, which code for the subunits of soluble guanylate cyclase. There was further support for the previously reported effects of variants in <i>NPR1</i> and protective effects of variants in <i>DBH</i>. An inframe deletion in <i>CACNA1D</i> with MAF = 0.005, rs72556363, is associated with modestly increased risk of hypertension. Other biologically plausible genes highlighted consist of <i>CSK</i>, <i>AGTR1</i>, <i>ZYX</i>, and <i>PREP</i>. All variants implicated were rare, and cumulatively they are not predicted to make a large contribution to the population risk of hypertension. <b><i>Conclusions:</i></b> This approach confirms and clarifies previously reported findings and also offers novel insights into biological processes influencing hypertension risk, potentially facilitating the development of improved therapeutic interventions. This research has been conducted using the UK Biobank Resource.

Macronutrient Intake and Risk of Dementia in Community-Dwelling Older Adults: A Nine-Year Follow-Up Cohort Study

2021 ◽  
pp. 1-14
Author(s):  
Xianwen Shang ◽  
Edward Hill ◽  
Zhuoting Zhu ◽  
Jiahao Liu ◽  
Zongyuan Ge ◽  
...  
Keyword(s):  
Protein Intake ◽  
Multivariable Analysis ◽  
Community Dwelling ◽  
Hospital Inpatient ◽  
Macronutrient Intake ◽  
Incident Dementia ◽  
Increased Risk ◽  
Reported Data ◽  
The Uk

Background: Little is known about the association between macronutrient intake and incident dementia. Objective: To identify an optimal range of macronutrient intake associated with reduced risk of dementia. Methods: Our analysis included 93,389 adults aged 60–75 years from the UK Biobank. Diet was assessed using a web-based 24-h recall questionnaire between 2009–2012. Dementia was ascertained using hospital inpatient, death records, and self-reported data up to January 2021. We calculated a macronutrient score based on associations between an individual’s macronutrient intake and incident dementia. Results: During a median follow-up of 8.7 years, 1,171 incident dementia cases were documented. We found U-shape relationships for carbohydrate, fat, and protein intake with incident dementia. Compared to individuals with optimal carbohydrate intake, those with high intake (HR (95%CI): 1.48(1.15–1.91)) but not low intake (1.19(0.89–1.57)) had a higher risk of dementia. In the multivariable analysis, a low-fat intake (HR (95%CI): 1.42(1.11–1.82)) was associated with a higher risk of all-cause dementia. After adjustment for covariates, a high (HR (95%CI): 1.41(1.09–1.83)) but not low protein intake (1.22(0.94–1.57)) was associated with an increased risk of dementia. Individuals in quintiles 3–5 of optimal macronutrient score had a lower risk of dementia compared with those in quintile 1 (HR (95%CI): 0.76(0.64–0.91) for quintile 3, 0.71(0.60–0.85) for quintile 4, 0.74(0.61–0.91) for quintile 5). The association between macronutrient score and incident dementia was significant across subgroups of age, gender, education, and smoking. Conclusion: Moderate intakes of carbohydrate, fat, and protein were associated with the lowest risk of incident dementia.

scholarly journals Analysis of 200,000 exome-sequenced UK Biobank subjects implicates genes involved in increased and decreased risk of hypertension

2021 ◽  
Author(s):  
David Curtis
Keyword(s):  
Rare Variants ◽  
Soluble Guanylate Cyclase ◽  
Therapeutic Interventions ◽  
Large Contribution ◽  
Protective Effects ◽  
Uk Biobank ◽  
Increased Risk ◽  
Higher Weights ◽  
The Uk ◽  
Diagnosis Of Hypertension

AbstractBackgroundPrevious analyses have identified common variants along with some specific genes and rare variants which are associated with risk of hypertension but much remains to be discovered.Methods and ResultsExome-sequenced UK Biobank participants were phenotyped based on having a diagnosis of hypertension or taking anti-hypertensive medication to produce a sample of 66,123 cases and 134,504 controls. Variants with minor allele frequency (MAF) < 0.01 were subjected to a gene-wise weighted burden analysis, with higher weights assigned to variants which are rarer and/or predicted to have more severe effects. Of 20,384 genes analysed, two genes were exome-wide significant,DNMT3AandFES. Also strongly implicated wereGUCY1A1andGUCY1B1, which code for the subunits of soluble guanylate cyclase. There was further support for the previously reported effects of variants inNPR1and protective effects of variants inDBH. An inframe deletion inCACNA1Dwith MAF = 0.005, rs72556363, is associated with modestly increased risk of hypertension. Other biologically plausible genes highlighted consist ofCSK, AGTR1, ZYXandPREP. All variants implicated were rare and cumulatively they are not predicted to make a large contribution to the population risk of hypertension.ConclusionsThis approach confirms and clarifies previously reported findings and also offers novel insights into biological processes influencing hypertension risk, potentially facilitating the development of improved therapeutic interventions. This research has been conducted using the UK Biobank Resource.

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 Cardiovascular-related deaths at the beginning of the COVID-19 outbreak: a prospective analysis based on the UK Biobank

BMJ Open ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. e046931
Author(s):  
Junren Wang ◽  
Jianwei Zhu ◽  
Huazhen Yang ◽  
Yao Hu ◽  
Yajing Sun ◽  
...  
Keyword(s):  
Primary Diagnosis ◽  
Secondary Outcome ◽  
Hospital Inpatient ◽  
Reference Period ◽  
Stress Reactions ◽  
Uk Biobank ◽  
The Uk ◽  
The Impact ◽  
Distinct Increase ◽  
Related Mortality

ObjectiveTo assess the impact of the COVID-19 outbreak on cardiovascular disease (CVD) related mortality and hospitalisation.DesignCommunity-based prospective cohort study.SettingThe UK Biobank.Participants421 372 UK Biobank participants who were registered in England and alive as of 1 January 2020.Primary and secondary outcome measuresThe primary outcome of interest was CVD-related death, which was defined as death with CVD as a cause in the death register. We retrieved information on hospitalisations with CVD as the primary diagnosis from the UK Biobank hospital inpatient data. The study period was 1 January 2020 to June 30 2020, and we used the same calendar period of the three preceding years as the reference period. In order to control for seasonal variations and ageing of the study population, standardised mortality/incidence ratios (SMRs/SIRs) with 95% CIs were used to estimate the relative risk of CVD outcomes during the study period, compared with the reference period.ResultsWe observed a distinct increase in CVD-related deaths in March and April 2020, compared with the corresponding months of the three preceding years. The observed number of CVD-related deaths (n=218) was almost double in April, compared with the expected number (n=120) (SMR=1.82, 95% CI 1.58 to 2.07). In addition, we observed a significant decline in CVD-related hospitalisations from March onwards, with the lowest SIR observed in April (0.45, 95% CI 0.41 to 0.49).ConclusionsThere was a distinct increase in the number of CVD-related deaths in the UK Biobank population at the beginning of the COVID-19 outbreak. The shortage of medical resources for hospital care and stress reactions to the pandemic might have partially contributed to the excess CVD-related mortality, underscoring the need of sufficient healthcare resources and improved instructions to the public about seeking healthcare in a timely way.

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.

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