scholarly journals Common conditions associated with hereditary haemochromatosis genetic variants: cohort study in UK Biobank

BMJ ◽  
2019 ◽  
pp. k5222 ◽  
Author(s):  
Luke C Pilling ◽  
Jone Tamosauskaite ◽  
Garan Jones ◽  
Andrew R Wood ◽  
Lindsay Jones ◽  
...  
Keyword(s):  
Cohort Study ◽  
Confidence Interval ◽  
Community Sample ◽  
Hospital Inpatient ◽  
Uk Biobank ◽  
European Descent ◽  
Hereditary Haemochromatosis ◽  
Condition Versus ◽  
Early Case

Abstract Objective To compare prevalent and incident morbidity and mortality between those with the HFE p.C282Y genetic variant (responsible for most hereditary haemochromatosis type 1) and those with no p.C282Y mutations, in a large UK community sample of European descent. Design Cohort study. Setting 22 centres across England, Scotland, and Wales in UK Biobank (2006-10). Participants 451 243 volunteers of European descent aged 40 to 70 years, with a mean follow-up of seven years (maximum 9.4 years) through hospital inpatient diagnoses and death certification. Main outcome measure Odds ratios and Cox hazard ratios of disease rates between participants with and without the haemochromatosis mutations, adjusted for age, genotyping array type, and genetic principal components. The sexes were analysed separately as morbidity due to iron excess occurs later in women. Results Of 2890 participants homozygous for p.C282Y (0.6%, or 1 in 156), haemochromatosis was diagnosed in 21.7% (95% confidence interval 19.5% to 24.1%, 281/1294) of men and 9.8% (8.4% to 11.2%, 156/1596) of women by end of follow-up. p.C282Y homozygous men aged 40 to 70 had a higher prevalence of diagnosed haemochromatosis (odds ratio 411.1, 95% confidence interval 299.0 to 565.3, P<0.001), liver disease (4.30, 2.97 to 6.18, P<0.001), rheumatoid arthritis (2.23, 1.51 to 3.31, P<0.001), osteoarthritis (2.01, 1.71 to 2.36, P<0.001), and diabetes mellitus (1.53, 1.16 to 1.98, P=0.002), versus no p.C282Y mutations (n=175 539). During the seven year follow-up, 15.7% of homozygous men developed at least one incident associated condition versus 5.0% (P<0.001) with no p.C282Y mutations (women 10.1% v 3.4%, P<0.001). Haemochromatosis diagnoses were more common in p.C282Y/p.H63D heterozygotes, but excess morbidity was modest. Conclusions In a large community sample, HFE p.C282Y homozygosity was associated with substantial prevalent and incident clinically diagnosed morbidity in both men and women. As p.C282Y associated iron overload is preventable and treatable if intervention starts early, these findings justify re-examination of options for expanded early case ascertainment and screening.

scholarly journals Clinical laboratory tests and five-year incidence of major depressive disorder: a prospective cohort study of 433,890 participants from the UK Biobank

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Michael Wainberg ◽  
Stefan Kloiber ◽  
Breno Diniz ◽  
Roger S. McIntyre ◽  
Daniel Felsky ◽  
...  
Keyword(s):  
Public Health ◽  
Major Depressive Disorder ◽  
Cohort Study ◽  
Confidence Interval ◽  
Depressive Disorder ◽  
Blood Cell ◽  
Biological Processes ◽  
Uk Biobank ◽  
Major Depressive ◽  
The Uk

AbstractPrevention of major depressive disorder (MDD) is a public health priority. Identifying biomarkers of underlying biological processes that contribute to MDD onset may help address this public health need. This prospective cohort study encompassed 383,131 white British participants from the UK Biobank with no prior history of MDD, with replication in 50,759 participants of other ancestries. Leveraging linked inpatient and primary care records, we computed adjusted odds ratios for 5-year MDD incidence among individuals with values below or above the 95% confidence interval (<2.5th or >97.5th percentile) on each of 57 laboratory measures. Sensitivity analyses were performed across multiple percentile thresholds and in comparison to established reference ranges. We found that indicators of liver dysfunction were associated with increased 5-year MDD incidence (even after correction for alcohol use and body mass index): elevated alanine aminotransferase (AOR = 1.35, 95% confidence interval [1.16, 1.58]), aspartate aminotransferase (AOR = 1.39 [1.19, 1.62]), and gamma glutamyltransferase (AOR = 1.52 [1.31, 1.76]) as well as low albumin (AOR = 1.28 [1.09, 1.50]). Similar observations were made with respect to endocrine dysregulation, specifically low insulin-like growth factor 1 (AOR = 1.34 [1.16, 1.55]), low testosterone among males (AOR = 1.60 [1.27, 2.00]), and elevated glycated hemoglobin (HbA1C; AOR = 1.23 [1.05, 1.43]). Markers of renal impairment (i.e. elevated cystatin C, phosphate, and urea) and indicators of anemia and macrocytosis (i.e. red blood cell enlargement) were also associated with MDD incidence. While some immune markers, like elevated white blood cell and neutrophil count, were associated with MDD (AOR = 1.23 [1.07, 1.42]), others, like elevated C-reactive protein, were not (AOR = 1.04 [0.89, 1.22]). The 30 significant associations validated as a group in the multi-ancestry replication cohort (Wilcoxon p = 0.0005), with a median AOR of 1.235. Importantly, all 30 significant associations with extreme laboratory test results were directionally consistent with an increased MDD risk. In sum, markers of liver and kidney dysfunction, growth hormone and testosterone deficiency, innate immunity, anemia, macrocytosis, and insulin resistance were associated with MDD incidence in a large community-based cohort. Our results support a contributory role of diverse biological processes to MDD onset.

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 CAUSES OF FRAILTY: GENETIC ANALYSIS IN 164,000 UK BIOBANK PARTICIPANTS

2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S222-S222
Author(s):  
Janice Atkins ◽  
Luke C Pilling ◽  
Dylan Williams ◽  
Juulia Jylhävä ◽  
David Melzer
Keyword(s):  
Risk Factors ◽  
Cardiovascular Disease ◽  
Mendelian Randomization ◽  
Frailty Index ◽  
Geriatric Syndrome ◽  
Uk Biobank ◽  
Genomewide Association Study ◽  
European Descent ◽  
Ongoing Work

Abstract Frailty is an important and common geriatric syndrome, yet the mechanisms are multifactorial and not well understood. The Frailty Index (FI) is based on the Rockwood Index for accumulation of deficits, and we aimed to use genetics to gain mechanistic insights for interventions to prevent and delay frailty in older people. We performed a genomewide association study in 60 to 70 year old UK Biobank participants of European descent (n=164,610). We identified 26 independent genetic signals at 24 loci associated with the FI. Several of these signals have previously been associated with traits such as cardiovascular disease, intelligence, and educational attainment, but 6 of the signals appear to be novel. We will also present the results of ongoing work both to identify causal risk factors for FI using Mendelian randomization methods, and replication and functional follow-up in the TwinGene cohort, at the meeting.

scholarly journals Follow-up of incidental pulmonary nodules and association with mortality in a safety-net cohort

Diagnosis ◽  
2019 ◽  
Vol 6 (4) ◽  
pp. 351-359 ◽  
Author(s):  
Jonathan S. Lee ◽  
Sarah Lisker ◽  
Eric Vittinghoff ◽  
Roy Cherian ◽  
David B. McCoy ◽  
...  
Keyword(s):  
Cohort Study ◽  
Confidence Interval ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Pulmonary Nodules ◽  
Safety Net ◽  
Mortality Rates ◽  
All Cause Mortality ◽  
Multivariable Models

Abstract Background Though incidental pulmonary nodules are common, rates of guideline-recommended surveillance and associations between surveillance and mortality are unclear. In this study, we describe adherence (categorized as complete, partial, late and none) to guideline-recommended surveillance among patients with incidental 5–8 mm pulmonary nodules and assess associations between adherence and mortality. Methods This was a retrospective cohort study of 551 patients (≥35 years) with incidental pulmonary nodules conducted from September 1, 2008 to December 31, 2016, in an integrated safety-net health network. Results Of the 551 patients, 156 (28%) had complete, 87 (16%) had partial, 93 (17%) had late and 215 (39%) had no documented surveillance. Patients were followed for a median of 5.2 years [interquartile range (IQR), 3.6–6.7 years] and 82 (15%) died during follow-up. Adjusted all-cause mortality rates ranged from 2.24 [95% confidence interval (CI), 1.24–3.25] deaths per 100 person-years for complete follow-up to 3.30 (95% CI, 2.36–4.23) for no follow-up. In multivariable models, there were no statistically significant associations between the levels of surveillance and mortality (p > 0.16 for each comparison with complete surveillance). Compared with complete surveillance, adjusted mortality rates were non-significantly increased by 0.45 deaths per 100 person-years (95% CI, −1.10 to 2.01) for partial, 0.55 (95% CI, −1.08 to 2.17) for late and 1.05 (95% CI, −0.35 to 2.45) for no surveillance. Conclusions Although guideline-recommended surveillance of small incidental pulmonary nodules was incomplete or absent in most patients, gaps in surveillance were not associated with statistically significant increases in mortality in a safety-net population.

scholarly journals Weight change over two years in people prescribed olanzapine, quetiapine and risperidone in UK primary care: Cohort study in THIN, a UK primary care database

2018 ◽  
Vol 32 (10) ◽  
pp. 1098-1103 ◽  
Author(s):  
David PJ Osborn ◽  
Irene Petersen ◽  
Nick Beckley ◽  
Kate Walters ◽  
Irwin Nazareth ◽  
...  
Keyword(s):  
Primary Care ◽  
Cohort Study ◽  
Weight Gain ◽  
Confidence Interval ◽  
Weight Change ◽  
Antipsychotic Treatment ◽  
Weight Changes ◽  
Baseline Weight ◽  
Care Database

Background: Follow-up studies of weight gain related to antipsychotic treatment beyond a year are limited in number. We compared weight change in the three most commonly prescribed antipsychotics in a representative UK General Practice database. Method: We conducted a cohort study in United Kingdom primary care records of people newly prescribed olanzapine, quetiapine or risperidone. The primary outcome was weight in each six month period for two years after treatment initiation. Weight changes were compared using linear regression, adjusted for age, baseline weight and diagnosis. Results: N = 6338 people received olanzapine, 12,984 quetiapine and 6556 risperidone. Baseline weight was lowest for men treated with olanzapine (80.8 kg versus 83.5 kg quetiapine, 82.0 kg risperidone) and women treated with olanzapine (67.7 kg versus 71.5 kg quetiapine 68.4 kg risperidone. Weight gain occurred during treatment with all three drugs. Compared with risperidone mean weight gain was higher with olanzapine (adjusted co-efficient +1.24 kg (95% confidence interval: 0.69–1.79 kg per six months) for men and +0.77 kg (95% confidence interval: 0.29–1.24 kg) for women). Weight gain with quetiapine was lower in unadjusted models compared with risperidone, but this difference was not significant after adjustment. Conclusion: Olanzapine is more commonly prescribed to people with lower weight. However, after accounting for baseline weight, age, sex and diagnosis, olanzapine is still associated with greater weight gain over two years than risperidone or quetiapine. Baseline weight does not ameliorate the risks of weight gain associated with antipsychotic medication. Weight gain should be assertively discussed and managed for people prescribed antipsychotics, especially olanzapine.

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 Cardiovascular Disease and All-Cause Mortality in Male Twins With Discordant Cardiorespiratory Fitness: A Nationwide Cohort Study

2020 ◽  
Vol 189 (10) ◽  
pp. 1114-1123
Author(s):  
Marcel Ballin ◽  
Anna Nordström ◽  
Peter Nordström
Keyword(s):  
Cardiovascular Disease ◽  
Cohort Study ◽  
Confidence Interval ◽  
Cardiorespiratory Fitness ◽  
Military Service ◽  
Lower Risk ◽  
Hazard Ratio ◽  
Familial Factors ◽  
All Cause Mortality

Abstract Whether genetic and familial factors influence the association between cardiorespiratory fitness (CRF) and cardiovascular disease (CVD) is unknown. Two cohorts were formed based on data from 1,212,295 men aged 18 years who were conscripted for military service in Sweden during 1972–1996. The first comprised 4,260 twin pairs in which the twins in each pair had different CRF (≥1 watt). The second comprised 90,331 nonsibling pairs with different CRF and matched on birth year and year of conscription. Incident CVD and all-cause mortality were identified using national registers. During follow-up (median 32 years), there was no difference in CVD and mortality between fitter twins and less fit twins (246 vs. 251 events; hazard ratio (HR) = 1.00, 95% confidence interval (CI): 0.83, 1.20). The risks were similar in twin pairs with ≥60-watt difference in CRF (HR = 0.96, 95% CI: 0.57, 1.64). In contrast, in the nonsibling cohort, fitter men had a lower risk of the outcomes than less fit men (4,444 vs. 5,298 events; HR = 0.83, 95% CI: 0.79, 0.86). The association was stronger in pairs with ≥60-watt difference in CRF (HR = 0.65, 95% CI: 0.59, 0.71). These findings indicate that genetic and familial factors influence the association of CRF with CVD and mortality.

scholarly journals Risk of cardiovascular disease after a diagnosis of common psychiatric disorders: a matched cohort study of disease susceptibility and progression trajectory in the UK Biobank

2021 ◽  
Author(s):  
Xin Han ◽  
Yu Zeng ◽  
Yanan Shang ◽  
Yao Hu ◽  
Can Hou ◽  
...  
Keyword(s):  
Myocardial Infarction ◽  
Acute Myocardial Infarction ◽  
Cohort Study ◽  
Psychiatric Disorders ◽  
Temporal Pattern ◽  
Disease Susceptibility ◽  
Matched Cohort ◽  
Uk Biobank ◽  
Psychiatry Disorders

Background: Whether associations between psychiatric disorders and cardiovascular diseases (CVDs) can be modified by disease susceptibility and the temporal pattern of these associated CVDs remain unknown. Methods: We conducted a matched cohort study of UK Biobank including 35,227 patients with common psychiatry disorders (anxiety, depression, and stress-related disorders) between 1997 and 2019, together with 176,135 sex- and birth year- individually matched unexposed individuals.Results: The mean age at the index date was 51.76 years, and 66.0% of participants were females. During a mean follow-up of 11.94 years, we observed an elevated risk of CVD among patients with studied psychiatry disorders, compared with matched unexposed individuals (hazard ratios [HRs]=1.16, 95% confidence interval [CI]: 1.14-1.19), especially during the first six months of follow-up (HR=1.59 [1.42-1.79]). To assess the modification role of disease susceptibility, we stratified analyses by family history of CVD and by CVD PRS, which obtained similar estimates between subgroups with different susceptibilities to CVD. We conducted trajectory analysis to visualize the temporal pattern of CVDs after common psychiatry disorders, identifying primary hypertension, acute myocardial infarction, and stroke as three main intermediate steps leading to further increased risk of other CVDs.Conclusions: The association between common psychiatry disorders and subsequent CVD is not modified by predisposition to CVD. Hypertension, acute myocardial infarction, and stroke are three initial CVDs linking psychiatric disorders to other CVD squeals, highlighting a need of timely intervention on these targets to prevent further CVD squeals among all individuals with common psychiatric disorders.Funding: This work is supported by the National Natural Science Foundation of China (No. 81971262 to HS), 1.3.5 project for disciplines of excellence, West China Hospital, Sichuan University (No. ZYYC21005 to HS), EU Horizon2020 Research and Innovation Action Grant (847776 to UV and FF).

scholarly journals Effect of dialysis modality on the survival of end-stage renal disease patients starting dialysis in Sabah from 2007 to 2017: a retrospective cohort study

2021 ◽  
Author(s):  
Thamron Keowmani ◽  
Anis Kausar Ghazali ◽  
Najib Majdi Yaacob ◽  
Koh Wei Wong
Keyword(s):  
Cohort Study ◽  
Peritoneal Dialysis ◽  
Confidence Interval ◽  
Renal Disease ◽  
End Stage Renal Disease ◽  
Retrospective Cohort ◽  
Dialysis Modality ◽  
Stage Renal Disease ◽  
End Stage

Background: The effect of dialysis modality on the survival of end-stage renal disease patients is a major public health interest. Methods: In this retrospective cohort study, all adult end-stage renal disease patients receiving dialysis treatment in Sabah between January 1, 2007 and December 31, 2017 as identified from the Malaysian Dialysis and Transplant Registry were evaluated and followed up through December 31, 2018. The endpoint was all-cause mortality. The observation time was defined as the time from the date of dialysis initiation after the onset of end-stage renal disease to whichever of the following that came first: date of death, date of transplantation, date of last follow-up, date of recovered kidney function, or December 31, 2018. Weighted Cox regression was used to estimate the effect of dialysis modality. Analyses were restricted to patients with complete data on all variables. Results: 1,837 patients began hemodialysis and 156 patients started with peritoneal dialysis, yielding 7,548.10 (potential median 5.48 years/person) and 747.98 (potential median 5.68 years/person) person-years of observation. 3.1% of patients were lost to follow-up. The median survival time was 5.8 years (95% confidence interval: 5.4, 6.3) among patients who started on hemodialysis and 7.0 years (95% confidence interval: 5.9, indeterminate) among those who started on peritoneal dialysis. The effect of dialysis modality was not significant after controlling for confounders. The average hazard ratio was 0.80 (95% confidence interval: 0.61, 1.05) with hemodialysis as a reference. Conclusion: There was no evidence of a difference in mortality between hemodialysis and peritoneal dialysis.

scholarly journals Use of high dose cyproterone acetate and risk of intracranial meningioma in women: cohort study

BMJ ◽  
2021 ◽  
pp. n37
Author(s):  
Alain Weill ◽  
Pierre Nguyen ◽  
Moujahed Labidi ◽  
Benjamin Cadier ◽  
Thibault Passeri ◽  
...  
Keyword(s):  
Cohort Study ◽  
Confidence Interval ◽  
Skull Base ◽  
Cumulative Dose ◽  
Cyproterone Acetate ◽  
Exposed Group ◽  
Additional Analysis ◽  
Control Group ◽  
High Dose

Abstract Objective To assess the risk of meningioma associated with use of high dose cyproterone acetate, a progestogen indicated for clinical hyperandrogenism. Design Observational cohort study. Setting Data from SNDS, the French administrative healthcare database, between 2007 and 2015. Participants 253 777 girls and women aged 7-70 years living in France who started cyproterone acetate between 2007 and 2014. Participants had at least one reimbursement for high dose cyproterone acetate and no history of meningioma or benign brain tumour, or long term disease status. Participants were considered to be exposed when they had received a cumulative dose of at least 3 g during the first six months (139 222 participants) and very slightly exposed (control group) when they had received a cumulative dose of less than 3 g (114 555 participants). 10 876 transgender participants (male to female) were included in an additional analysis. Main outcome measure Surgery (resection or decompression) or radiotherapy for one or more intracranial meningiomas. Results Overall, 69 meningiomas in the exposed group (during 289 544 person years of follow-up) and 20 meningiomas in the control group (during 439 949 person years of follow-up) were treated by surgery or radiotherapy. The incidence of meningioma in the two groups was 23.8 and 4.5 per 100 000 person years, respectively (crude relative risk 5.2, 95% confidence interval 3.2 to 8.6; adjusted hazard ratio 6.6, 95% confidence interval 4.0 to 11.1). The adjusted hazard ratio for a cumulative dose of cyproterone acetate of more than 60 g was 21.7 (10.8 to 43.5). After discontinuation of cyproterone acetate for one year, the risk of meningioma in the exposed group was 1.8-fold higher (1.0 to 3.2) than in the control group. In a complementary analysis, 463 women with meningioma were observed among 123 997 already using cyproterone acetate in 2006 (risk of 383 per 100 000 person years in the group with the highest exposure in terms of cumulative dose). Meningiomas located in the anterior skull base and middle skull base, particularly the medial third of the middle skull base, involving the spheno-orbital region, appeared to be specific to cyproterone acetate. An additional analysis of transgender participants showed a high risk of meningioma (three per 14 460 person years; 20.7 per 100 000 person years). Conclusions A strong dose-effect relation was observed between use of cyproterone acetate and risk of intracranial meningiomas. A noticeable reduction in risk was observed after discontinuation of treatment.

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