scholarly journals Association of social isolation, loneliness, and genetic risk with incidence of dementia: UK Biobank cohort study

2020 ◽  
Author(s):  
Marko Elovainio ◽  
Jari Lahti ◽  
Matti Pirinen ◽  
Laura Pulkki-Råback ◽  
Anni Malmberg ◽  
...  
Keyword(s):  
Cohort Study ◽  
Social Isolation ◽  
Genetic Risk ◽  
Significant Risk ◽  
Polygenic Risk Score ◽  
List Type ◽  
Uk Biobank ◽  
High Genetic Risk ◽  
Increased Risk ◽  
Socially Isolated

ObjectiveTo examine the associations of social isolation and loneliness with incident dementia by level of genetic risk.DesignProspective population-based cohort study.Setting and participants155 074 men and women (mean age 64.1, SD 2.9 years) from the UK Biobank Study, recruited between 2006 and 2010.Main exposuresSelf-reported social isolation and loneliness, and polygenic risk score for Alzheimer’s disease with low (lowest quintile), intermediate (quintiles 2 to 4), and high (highest quintile) risk categories.Main outcomeIncident all-cause dementia ascertained using electronic health records.ResultsOverall, 8.6% of participants reported that they were socially isolated and 5.5% were lonely. During a mean follow-up of 8.8 years (1.36 million person-years), 1444 (0.9% of the total sample) were diagnosed with dementia. Social isolation, but not loneliness, was associated with increased risk of dementia (hazard ratio 1.62, 95% confidence interval 1.38 to 1.90). Of the participants who were socially isolated and had high genetic risk, 4.2% (2.9% to 5.5%) were estimated to develop dementia compared with 3.1% (2.7% to 3.5%) in participants who were not socially isolated but had high genetic risk. The corresponding estimated incidence in the socially isolated and not isolated were 3.9% (3.1% to 4.6%) and 2.5% (2.2% to 2.6%) in participants with intermediate genetic risk.ConclusionSocially isolated individuals are at increased risk of dementia at all levels of genetic risk.What is already known on this topicSocial isolation and loneliness have been associated with increased risk of dementiaIt is not known whether this risk is modified or confounded by genetic risk of dementiaWhat this study addsThis is the first study to show that social isolation is associated with increased risk of dementia across the spectrum of genetic riskLoneliness, although considered as a significant risk for multiple health problems, seems to be associated with dementia only when combined with high genetic risk

scholarly journals Genetic risk, incident stroke, and the benefits of adhering to a healthy lifestyle: cohort study of 306 473 UK Biobank participants

BMJ ◽  
2018 ◽  
pp. k4168 ◽  
Author(s):  
Loes CA Rutten-Jacobs ◽  
Susanna C Larsson ◽  
Rainer Malik ◽  
Kristiina Rannikmäe ◽  
Cathie L Sudlow ◽  
...  
Keyword(s):  
Cohort Study ◽  
Risk Score ◽  
Genetic Risk ◽  
Cox Regression ◽  
Healthy Lifestyle ◽  
Lifestyle Factors ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Polygenic Risk ◽  
Increased Risk

AbstractObjectiveTo evaluate the associations of a polygenic risk score and healthy lifestyle with incident stroke.DesignProspective population based cohort study.SettingUK Biobank Study, UK.Participants306 473 men and women, aged 40-73 years, recruited between 2006 and 2010.Main outcome measureHazard ratios for a first stroke, estimated using Cox regression. A polygenic risk score of 90 single nucleotide polymorphisms previously associated with stroke was constructed at P<1×10−5to test for an association with incident stroke. Adherence to a healthy lifestyle was determined on the basis of four factors: non-smoker, healthy diet, body mass index <30 kg/m2, and regular physical exercise.ResultsDuring a median follow-up of 7.1 years (2 138 443 person years), 2077 incident strokes (1541 ischaemic stroke, 287 intracerebral haemorrhage, and 249 subarachnoid haemorrhage) were ascertained. The risk of incident stroke was 35% higher among those at high genetic risk (top third of polygenic score) compared with those at low genetic risk (bottom third): hazard ratio 1.35 (95% confidence interval 1.21 to 1.50), P=3.9×10−8. Unfavourable lifestyle (0 or 1 healthy lifestyle factors) was associated with a 66% increased risk of stroke compared with a favourable lifestyle (3 or 4 healthy lifestyle factors): 1.66 (1.45 to 1.89), P=1.19×10−13. The association with lifestyle was independent of genetic risk stratums.ConclusionIn this cohort study, genetic and lifestyle factors were independently associated with incident stroke. These results emphasise the benefit of entire populations adhering to a healthy lifestyle, independent of genetic risk.

Relationships of sleep traits with lung cancer risk: a prospective cohort study in UK Biobank

SLEEP ◽  
2021 ◽  
Author(s):  
Junxing Xie ◽  
Meng Zhu ◽  
Mengmeng Ji ◽  
Jingyi Fan ◽  
Yanqian Huang ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Cancer Risk ◽  
Sleep Duration ◽  
Genetic Risk ◽  
Lung Cancer Risk ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
High Genetic Risk ◽  
Sleep Behaviors ◽  
Incident Cases

Abstract Study objectives To prospectively investigate the association between sleep traits and lung cancer risk, accounting for the interactions with genetic predisposition of lung cancer. Methods We included 469,691 individuals free of lung cancer at recruitment from UK Biobank, measuring sleep behaviors with a standardized questionnaire and identifying incident lung cancer cases through linkage to national cancer and death registries. We estimated multivariable adjusted hazard ratios (HR) for lung cancer (2,177 incident cases) across four sleep traits (sleep duration, chronotype, insomnia and snoring), and examined the interaction and joint effects with a lung cancer polygenic risk score. Results A U-shaped association was observed for sleep duration and lung cancer risk, with a 18% higher risk (95% confidence interval (CI): 1.07-1.30) for short sleepers and a 17% higher risk (95%CI: 1.02-1.34) for long sleepers compared with normal sleepers (7-8 h/day). Evening preference was associated with elevated lung cancer risk compared with morning preference (HR: 1.25; 95%CI: 1.07-1.46), but no association was found for insomnia or snoring. Compared to participants with favorable sleep traits and low genetic risk, those with both unfavorable sleep duration (&lt;7 hours or &gt;8 hours) or evening preference and high genetic risk showed the greatest lung cancer risk (HRsleep duration: 1.83; 95%CI: 1.47-2.27; HRchronotype: 1.85; 95%CI: 1.34-2.56). Conclusions Both unfavorable sleep duration and evening chronotype were associated with increased lung cancer incidence, especially for those with low to moderate genetic risk. These results indicate that sleep behaviors as modifiable risk factors may have potential implications for lung cancer risk.

scholarly journals Modification effect of ideal cardiovascular health metrics on genetic association with incident heart failure in the China Kadoorie Biobank and the UK Biobank

BMC Medicine ◽  
2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Ruotong Yang ◽  
Jun Lv ◽  
Canqing Yu ◽  
Yu Guo ◽  
Pei Pei ◽  
...  
Keyword(s):  
Heart Failure ◽  
Genetic Association ◽  
Genetic Risk ◽  
Lower Risk ◽  
Cardiovascular Health ◽  
Polygenic Risk Score ◽  
Uk Biobank ◽  
Additive Interaction ◽  
High Genetic Risk ◽  
Modification Effect

Abstract Background Both genetic and cardiovascular factors contribute to the risk of developing heart failure (HF), but whether idea cardiovascular health metrics (ICVHMs) offset the genetic association with incident HF remains unclear. Objectives To investigate the genetic association with incident HF as well as the modification effect of ICVHMs on such genetic association in Chinese and British populations. Methods An ICVHMs based on smoking, drinking, physical activity, diets, body mass index, waist circumference, blood pressure, blood glucose, and blood lipids, and a polygenic risk score (PRS) for HF were constructed in the China Kadoorie Biobank (CKB) of 96,014 participants and UK Biobank (UKB) of 335,782 participants which were free from HF and severe chronic diseases at baseline. Results During the median follow-up of 11.38 and 8.73 years, 1451 and 3169 incident HF events were documented in CKB and UKB, respectively. HF risk increased monotonically with the increase of PRS per standard deviation (CKB: hazard ratio [HR], 1.19; 95% confidence interval [CI], 1.07, 1.32; UKB: 1.07; 1.03, 1.11; P for trend < 0.001). Each point increase in ICVHMs was associated with 15% and 20% lower risk of incident HF in CKB (0.85; 0.81, 0.90) and UKB (0.80; 0.77, 0.82), respectively. Compared with unfavorable ICVHMs, favorable ICVHMs was associated with a lower HF risk, with 0.71 (0.44, 1.15), 0.41 (0.22, 0.77), and 0.48 (0.30, 0.77) in the low, intermediate, and high genetic risk in CKB and 0.34 (0.26, 0.44), 0.32 (0.25, 0.41), and 0.37 (0.28, 0.47) in UKB (P for multiplicative interaction > 0.05). Participants with low genetic risk and favorable ICVHMs, as compared with high genetic risk and unfavorable ICVHMs, had 56~72% lower risk of HF (CKB 0.44; 0.28, 0.70; UKB 0.28; 0.22, 0.37). No additive interaction between PRS and ICVHMs was observed (relative excess risk due to interaction was 0.05 [−0.22, 0.33] in CKB and 0.04 [−0.14, 0.22] in UKB). Conclusions In CKB and UKB, genetic risk and ICVHMs were independently associated with the risk of incident HF, which suggested that adherence to favorable cardiovascular health status was associated with a lower HF risk among participants with all gradients of genetic risk.

Associations of genetic risk and smoking with incident chronic obstructive pulmonary disease

2021 ◽  
pp. 2101320
Author(s):  
Pei-Dong Zhang ◽  
Xi-Ru Zhang ◽  
Ao Zhang ◽  
Zhi-Hao Li ◽  
Dan Liu ◽  
...  
Keyword(s):  
Chronic Obstructive Pulmonary Disease ◽  
Pulmonary Disease ◽  
Genetic Risk ◽  
Chronic Obstructive ◽  
Polygenic Risk Score ◽  
Obstructive Pulmonary Disease ◽  
Current Smoking ◽  
High Genetic Risk ◽  
Genome Wide ◽  
Genome Wide Significance

BackgroundGenetic and smoking contribute to chronic obstructive pulmonary disease (COPD), but whether a combined polygenic risk score (PRS) is associated with incident COPD and whether it has a synergistic effect on the smoking remains unclear. We aimed to investigate the association of PRS with COPD and explore whether smoking behaviors could modify such association.MethodsMultivariable Cox proportional models were used to estimate hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association of the PRS and smoking with COPD.ResultsThe study included 439 255 participants (mean age 56.5; 53.9% female), with a median follow-up of 9.0 years. The PRSlasso containing 2.5 million variants showed better discrimination and a stronger association for incident COPD than the PRS279 containing 279 genome-wide significance variants. Compared with the low genetic risk, the HRs of the medium and high genetic risk were 1.39 (95% CI, 1.31–1.48) and 2.40 (95% CI, 2.24–2.56), respectively. The HR of high genetic risk and current smoking was 11.62 (95% CI, 10.31–13.10) times of low genetic risk and never smoking. There were significant interactions between the PRSlasso and smoking status for incident COPD (p for interaction<0.001). From low genetic risk to high genetic risk, the HRs of current smoking increased from 4.32 (95% CI, 3.69–5.06) to 6.89 (95% CI, 6.21–7.64), and the population-attributable risks of smoking increased from 42.7% to 61.1%.ConclusionPRS constructed from millions of variants below genome-wide significance showed significant associations with incident COPD. Participants with a high genetic risk may be more susceptible to developing COPD when exposed to smoking.

scholarly journals Polygenic Susceptibility of Aortic Aneurysms Associates to the Diameter of the Aneurysm Sac: the Aneurysm-Express Biobank Cohort

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Constance J. H. C. M. van Laarhoven ◽  
Jessica van Setten ◽  
Joost A. van Herwaarden ◽  
Gerard Pasterkamp ◽  
Dominique P. V. de Kleijn ◽  
...  
Keyword(s):  
Genetic Risk ◽  
Association Studies ◽  
Significant Risk ◽  
Aortic Aneurysms ◽  
Polygenic Risk Score ◽  
Genome Wide Association Studies ◽  
Risk Variants ◽  
Genome Wide ◽  
Best Fit ◽  
Genetic Risk Variants

AbstractRecent genome-wide association studies (GWAS) have discovered ten genetic risk variants for abdominal aortic aneurysms (AAA). To what extent these genetic variants contribute to the pathology of aneurysms is yet unknown. The present study aims to investigate whether genetic risk variants are associated with three clinical features: diameter of aneurysm sac, type of artery and aneurysm related-symptoms in aortic and peripheral aneurysm patients. Aneurysm tissue of 415 patients included in the Aneurysm-Express biobank was used. A best-fit polygenic risk score (PRS) based on previous GWAS effect estimates was modeled for each clinical phenotype. The best-fit PRS (including 272 variants at PT = 0.01015) showed a significant correlation with aneurysm diameter (R2 = 0.019, p = 0.001). No polygenic association was found with clinical symptoms or artery type. In addition, the ten genome-wide significant risk variants for AAA were tested individually, but no associations were observed with any of the clinical phenotypes. All models were corrected for confounders and data was normalized. In conclusion, a weighted PRS of AAA susceptibility explained 1.9% of the phenotypic variation (p = 0.001) in diameter in aneurysm patients. Given our limited sample size, future biobank collaborations need to confirm a potential causal role of susceptibility variants on aneurysmal disease initiation and progression.

Diabetes After Hormone Therapy in Breast Cancer Survivors: A Case-Cohort Study

2018 ◽  
Vol 36 (20) ◽  
pp. 2061-2069 ◽  
Author(s):  
Rola Hamood ◽  
Hatem Hamood ◽  
Ilya Merhasin ◽  
Lital Keinan-Boker
Keyword(s):  
Breast Cancer ◽  
Cohort Study ◽  
Cancer Survivors ◽  
Hormone Therapy ◽  
Breast Cancer Survivors ◽  
Significant Risk ◽  
Diabetes Risk ◽  
Adverse Outcomes ◽  
Lifestyle Modifications ◽  
Increased Risk

Purpose Breast cancer treatments have been associated with an increased risk of multiple health-related adverse outcomes, but the relationship with diabetes remains unclear. This study investigated the association between hormone therapy and diabetes risk in breast cancer survivors. Patients and Methods We performed a case-cohort study of 2,246 female survivors recruited from the Leumit health care fund who were diagnosed with primary nonmetastatic invasive breast cancer in 2002 through 2012. A 20% random subcohort was sampled at baseline, and all diabetes cases were identified. Adjusted hazard ratios (HRs) with 95% CIs were estimated by weighted Cox proportional hazards regression models. Results Of 2,246 breast cancer survivors, 324 developed diabetes over a mean follow-up of 5.9 years. The crude cumulative incidence of diabetes that accounted for death as a competing risk was 20.9% (95% CI, 18.3% to 23.7%). In multivariable-adjusted models, hormone therapy was associated with increased diabetes risk (HR, 2.40; 95% CI, 1.26 to 4.55; P = .008). The hazard for tamoxifen use (HR, 2.25; 95% CI, 1.19 to 4.26; P = .013) was less pronounced than the use of aromatase inhibitors (HR, 4.27, 95% CI, 1.42 to 12.84; P = .010). Conclusion Active hormone therapy is a significant risk factor of diabetes among breast cancer survivors. Although cessation of treatment is not recommended because the survival benefits of hormone therapy outweigh the risks, preventive strategies aimed at lifestyle modifications may minimize the risk.

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.

scholarly journals Child dysentery in the Limpopo Valley: a cohort study of water, sanitation and hygiene risk factors

2009 ◽  
Vol 7 (2) ◽  
pp. 259-266 ◽  
Author(s):  
Stephen W. Gundry ◽  
James A. Wright ◽  
Ronán M. Conroy ◽  
Martella Du Preez ◽  
Bettina Genthe ◽  
...  
Keyword(s):  
Risk Factors ◽  
Water Quality ◽  
Drinking Water ◽  
Cohort Study ◽  
Significant Risk ◽  
Watery Diarrhoea ◽  
Relative Risk Ratio ◽  
Source Water ◽  
Sanitation And Hygiene ◽  
Increased Risk

The objective of this cohort study was to assess risk factors for child dysentery and watery diarrhoea. The study participants consisted of 254 children aged 12–24 months in rural South Africa and Zimbabwe in households where drinking water was collected from communal sources. The main outcome measure was the most severe diarrhoea episode: dysentery, watery diarrhoea or none. For dysentery, drinking water from sources other than standpipes had a relative risk ratio of 3.8 (95% CI 1.5–9.8). Poor source water quality, as indicated by Escherichia coli counts of 10 or more cfu 100 ml−1, increased risk by 2.9 (1.5–5.7). There were no other significant risk factors for dysentery and none for watery diarrhoea. In this study, endemic dysentery is associated only with faecal contamination of source water. Sources other than standpipes, including improved groundwater, are of greater risk. Remediation of water quality by treatment at source or in the household will be required to achieve access to safe drinking water in accordance with the 7th Millennium Development Goal.

Bed Occupancy Rates and Hospital-Acquired Clostridium difficile Infection: A Cohort Study

2013 ◽  
Vol 34 (10) ◽  
pp. 1062-1069 ◽  
Author(s):  
Lauren C. Ahyow ◽  
Paul C. Lambert ◽  
David R. Jenkins ◽  
Keith R. Neal ◽  
Martin Tobin
Keyword(s):  
Cohort Study ◽  
Clostridium Difficile ◽  
Significant Risk ◽  
Organizational Factors ◽  
Economic Benefits ◽  
Bed Occupancy ◽  
Increased Risk ◽  
Hospital Acquired ◽  
Occupancy Rates ◽  
Bed Occupancy Rates

Background.An emergent strain (ribotype 027) of Clostridium difficile infection (CDI) has been implicated in epidemics worldwide. Organizational factors such as bed occupancy have been associated with an increased incidence of CDI; however, the data are sparse, and the association has not been widely demonstrated. We investigated the association of bed occupancy and CDI within a large hospital organization in the United Kingdom.Objective.To establish whether bed occupancy rates are a significant risk factor for CDI in the general ward setting.Methods.A retrospective cohort study was carried out on data from 2006 to 2008. Univariate and multivariate Cox regression modeling was used to examine the strength and significance of the associations. Variables included patient characteristics, antibiotic policy exposure, case mix, and bed occupancy rates.Results.A total of 1,589 cases of hospital-acquired CDI were diagnosed (1.7% of admissions), with an overall infection rate of 2.16 per 1,000 patient-days. Median bed occupancy was 93.3% (interquartile range, 83.3%–100%) Univariate and multivariate analyses showed positive and statistically significant associations. In the adjusted model, patients on wards with occupancy rates of 80%–89.9% had rates of CDI that were 56% higher (hazard ratio, 1.56 [95% confidence interval, 1.18–2.04]; P<.001) compared with baseline (0%–69.9% occupancy). CDI rates were 55% higher for patients on wards with maximal bed occupancy (100%).Conclusions.There is strong evidence of an association between high bed occupancy and CDI. Without effective interventions at high levels of bed occupancy, the economic benefits sought from reducing bed numbers may be negated by the increased risk of CDI.

scholarly journals Genetic risk for coronary heart disease alters the influence of Alzheimer’s genetic risk on mild cognitive impairment

2018 ◽  
Author(s):  
Jeremy A. Elman ◽  
Matthew S. Panizzon ◽  
Mark W. Logue ◽  
Nathan A. Gillespie ◽  
Michael C. Neale ◽  
...  
Keyword(s):  
Cognitive Impairment ◽  
Mild Cognitive Impairment ◽  
Genetic Risk ◽  
Early Stage ◽  
Case Fatality ◽  
Polygenic Risk Score ◽  
Protective Effects ◽  
Increased Risk ◽  
Incident Cases ◽  
The Impact

ABSTRACTBACKGROUNDAlzheimer’s disease (AD) is under considerable genetic influence. However, known susceptibility loci only explain a modest proportion of variance in disease outcomes. This small proportion could occur if the etiology of AD is heterogeneous. We previously found that an AD polygenic risk score (PRS) was significantly associated with mild cognitive impairment (MCI), an early stage of AD. Poor cardiovascular health is also associated with increased risk for AD and has been found to interact with AD pathology. Conditions such as coronary artery disease (CAD) are also heritable, and may contribute to heterogeneity if there are interactions of genetic risk for these conditions as there is phenotypically. However, case-control designs based on prevalent cases of a disease with relatively high case-fatality rate such as CAD may be biased toward individuals who have long post-event survival times and may therefore also identify loci with protective effects.METHODSWe compared interactions between an AD-PRS and two CAD-PRSs, one based on a GWAS of incident cases and one on prevalent cases, on MCI status in 1,209 individuals.RESULTSAs expected, the incidence-based CAD-PRS interacts with the AD-PRS to further increase MCI risk. Conversely, higher prevalence-based CAD-PRSs reduced the effect of AD genetic risk on MCI status.CONCLUSIONSThese results demonstrate: i) the utility of including multiple PRSs and their interaction effects; ii) how genetic risk for one disease may modify the impact of genetic risk for another; and iii) the importance of considering ascertainment procedures of GWAS being used for genetic risk prediction.

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