Background
Previous studies have reported Blood type O to confer a lower risk of SARS‐CoV‐2 infection, while secretor status and other blood groups have been suspected to have a similar effect as ...well.
Study design and methods
To determine whether any other blood groups influence testing positive for SARS‐CoV‐2, COVID‐19 severity, or prolonged COVID‐19, we used a large cohort of 650,156 Danish blood donors with varying available data for secretor status and blood groups ABO, Rh, Colton, Duffy, Diego, Dombrock, Kell, Kidd, Knops, Lewis, Lutheran, MNS, P1PK, Vel, and Yt.
Of these, 36,068 tested positive for SARS‐CoV‐2 whereas 614,088 tested negative between 2020‐02‐17 and 2021‐08‐04. Associations between infection and blood groups were assessed using logistic regression models with sex and age as covariates.
Results
The Lewis blood group antigen Lea displayed strongly reduced SARS‐CoV‐2 susceptibility OR 0.85 CI0.79–0.93 p < .001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI1.06–1.14 p < .001, 1.17 CI1.14–1.2 p < .001, and 1.2 CI1.14–1.26 p < .001, respectively. No susceptibility associations were found for the other 13 blood groups investigated. There was no association between any blood groups and COVID‐19 hospitalization or long COVID‐19. No secretor status associations were found.
Discussion
This study uncovers a new association to reduced SARS‐CoV‐2 susceptibility for Lewis type Lea and confirms the previous link to blood group O. The new association to Lea could be explained by a link between mucosal microbiome and SARS‐CoV‐2.
The pathophysiology of xerosis depends on extrinsic and intrinsic exposures. Residential hard water may constitute such an exposure. To estimate the prevalence of xerosis and to compare water ...hardness exposure in blood donors with and without xerosis. In this retrospective cohort study in 2018-2019, blood donors with self-reported moderately or severely dry skin were compared to blood donors without dry skin. Blood donors with ichthyosis, lichen planus and psoriasis were excluded. Water hardness data was collected from the Geology Survey of Denmark and Greenland. Overall, 4,748 of 30,721 (15.5%; 95% confidence interval 15.1-15.9%) blood donors had xerosis. After excluding blood donors with ichthyosis, lichen planus and psoriasis, 4,416 blood donors (2,559 females; median age 38.4 years interquartile range 28.0-49.8; 700 smokers) remained in this study. Water softer than 12-24 degrees Deutsche härte was associated with decreased probability of xerosis (odds ratio 0.83; 95% confidence interval 0.74-0.94) and water harder than 12-24 degrees Deutsche härte was associated with increased probability of xerosis (odds ratio 1.22; 95% confidence interval 1.03-1.45). The association between water hardness and xerosis remained significant after excluding blood donors with dermatitis. Water hardness is associated with xerosis independent of other dermatoses.
Genetic insight into sick sinus syndrome Thorolfsdottir, Rosa B; Sveinbjornsson, Gardar; Aegisdottir, Hildur M ...
European heart journal,
05/2021, Letnik:
42, Številka:
20
Journal Article
Recenzirano
Odprti dostop
Abstract
Aims
The aim of this study was to use human genetics to investigate the pathogenesis of sick sinus syndrome (SSS) and the role of risk factors in its development.
Methods and results
We ...performed a genome-wide association study of 6469 SSS cases and 1 000 187 controls from deCODE genetics, the Copenhagen Hospital Biobank, UK Biobank, and the HUNT study. Variants at six loci associated with SSS, a reported missense variant in MYH6, known atrial fibrillation (AF)/electrocardiogram variants at PITX2, ZFHX3, TTN/CCDC141, and SCN10A and a low-frequency (MAF = 1.1–1.8%) missense variant, p.Gly62Cys in KRT8 encoding the intermediate filament protein keratin 8. A full genotypic model best described the p.Gly62Cys association (P = 1.6 × 10−20), with an odds ratio (OR) of 1.44 for heterozygotes and a disproportionally large OR of 13.99 for homozygotes. All the SSS variants increased the risk of pacemaker implantation. Their association with AF varied and p.Gly62Cys was the only variant not associating with any other arrhythmia or cardiovascular disease. We tested 17 exposure phenotypes in polygenic score (PGS) and Mendelian randomization analyses. Only two associated with the risk of SSS in Mendelian randomization, AF, and lower heart rate, suggesting causality. Powerful PGS analyses provided convincing evidence against causal associations for body mass index, cholesterol, triglycerides, and type 2 diabetes (P > 0.05).
Conclusion
We report the associations of variants at six loci with SSS, including a missense variant in KRT8 that confers high risk in homozygotes and points to a mechanism specific to SSS development. Mendelian randomization supports a causal role for AF in the development of SSS.
Graphical Abstract
Summary of genetic insight into the pathogenesis of SSS and the role of risk factors in its development. Variants at six loci (named by corresponding gene names) were identified through GWAS and their unique phenotypic associations provide insight into distinct pathways underlying SSS. Investigation of the role of risk factors in SSS development supported a causal role for AF and heart rate and provided convincing evidence against causality for BMI, cholesterol (HDL and non-HDL), triglycerides and T2D. Mendelian randomization did not support causality for CAD, ischaemic stroke, heart failure, PR interval or QRS duration (not shown in figure). Red and blue arrows represent positive and negative associations, respectively.
ObjectivesTo examine the level of loneliness experienced during the COVID-19 pandemic in Denmark and to identify associated behavioural patterns and demographic factors.DesignCross-sectional cohort ...study.SettingIncludes Danish active and former blood donors.ParticipantsA questionnaire was sent to 124 307 active and former blood donors, of these a total of 50 968 participants completed the study questionnaire (response rate=41%).Primary and secondary outcome measuresSubjective experience of loneliness was measured using the 3-item University of California, Los Angeles Loneliness Scale (UCLA-3). Besides the UCLA-3, the respondents answered items on sociodemographic and economic characteristics, items on precautionary measures taken to avoid COVID-19 infection as well as on COVID-19 anxiety.ResultsThe participants indicated their experienced level of loneliness both before and during the pandemic. Comparing the two reports yielded a mean increase in loneliness scores of 14.1% (p<0.001). Exploratory factor analysis identified the factor well-being, which comprised three questionnaire items related to emotional heath, physical health and happiness. A high score on the factor well-being was associated with reduced levels of loneliness (coefficient=−0.47, 95% CI −0.49 to −0.46)). Furthermore, women were more likely than men to have experienced increased levels of loneliness during the pandemic (coefficient=0.27, 95% CI 0.25 to 0.29). Furthermore, a negative correlation between higher age and change in loneliness score was observed.ConclusionsThe findings document an increase in the level of experienced loneliness during the COVID-19 pandemic, particularly affecting individuals with low well-being, women and younger individuals.
A few studies have described an increased prevalence of skin infections in individuals with hyperhidrosis compared to others. However, it remains uncertain whether hyperhidrosis is an independent ...risk factor for skin infections.
To compare the risk of skin infections in individuals with and without hyperhidrosis.
In this retrospective cohort study, data on hyperhidrosis were collected from the Danish Blood Donor Study. Blood donors included in 2010-2019 were followed from inclusion until December 2019. Data on redeemed prescriptions against skin infections were collected from the National Prescription Register. The intensity of prescription-use by hyperhidrosis status was assessed in Andersen-Gill models.
Overall, 4,176 (9.6%) of 43,477 blood donors had self-reported hyperhidrosis and 437 (0.34%) of 127,823 blood donors had hospital diagnosed hyperhidrosis. Self-reported hyperhidrosis was associated with the use of antibiotic prescriptions (adjusted hazard ratio = 1.21; 95% confidence interval 1.00-1.45, p = 0.047). Hospital diagnosed hyperhidrosis was associated with the use of antibiotic (adjusted hazard ratio = 1.33; 95% confidence interval 1.03-1.68, p = 0.028) and topical antifungal prescriptions (adjusted hazard ratio = 1.43; 95% confidence interval 1.04-1.97, p = 0.027).
Hyperhidrosis is associated with the use of prescriptions for antibiotics and topical antifungals. This suggests a clinically relevant association between hyperhidrosis and skin infections.
Abstract Objective Restless legs syndrome (RLS) is a neurological sensorimotor disorder characterized by uncomfortable sensations in the legs. RLS often occurs as a comorbid condition. Besides an ...increased risk of iron deficiency, blood donors are considered to be generally healthy. Blood donors are therefore an ideal population for studying factors associated with RLS occurrence, herein the role of iron. It is suggested that RLS is linked to sex, age, low socioeconomic status, unhealthy lifestyle, and iron deficiency. The objective of this study is therefore to estimate the RLS prevalence and identify associated biological, sociodemographic, economic, and lifestyle factors in a population of blood donors. Methods A total of 13,448 blood donors enrolled in the Danish Blood Donor Study from May 2015 to May 2016. RLS cases were identified using the validated Cambridge–Hopkins RLS-questionnaire. Logistic regression models were applied to assess the relationship between RLS and data on socially related factors collected using questionnaires and population registers. Results In this study, 7.2% women and 4.5% men were classified with RLS. RLS was associated with: female sex, high age, smoking, frequent alcohol consumption, and low education. RLS-related symptoms were associated with obesity, parity and donation intensity 3 years prior to inclusion among women. RLS was not related to: reduced plasma ferritin, employment status, and income. Conclusions RLS is a frequent disorder in otherwise healthy individuals. The associations discovered in this study can be utilized in preventing or reducing RLS symptoms.
Many sequence variants have additive effects on blood lipid levels and, through that, on the risk of coronary artery disease (CAD). We show that variants also have non-additive effects and interact ...to affect lipid levels as well as affecting variance and correlations. Variance and correlation effects are often signatures of epistasis or gene-environmental interactions. These complex effects can translate into CAD risk. For example, Trp154Ter in FUT2 protects against CAD among subjects with the A1 blood group, whereas it associates with greater risk of CAD in others. His48Arg in ADH1B interacts with alcohol consumption to affect lipid levels and CAD. The effect of variants in TM6SF2 on blood lipids is greatest among those who never eat oily fish but absent from those who often do. This work demonstrates that variants that affect variance of quantitative traits can allow for the discovery of epistasis and interactions of variants with the environment.
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•Sequence variants can have complex effects on lipid levels through interactions•Variants at FUT2 and ABO interact on blood lipid levels and coronary artery disease•Alcohol consumption modifies the effect of a variant in ADH1B on lipids and CAD•Blood lipid composition in APOE-ε2 homozygotes differs substantially from others
Epistatic interactions between variants and gene-environment interactions can have complex phenotypic effects. By using blood lipid data from 743,736 individuals from three populations, it was shown here how these intricate interactions can have large effects on lipid levels and consequently coronary artery disease risk.
There is a gap in knowledge about the effects of smoking on overall infection risk in otherwise healthy populations, possibly leading to underestimation of the dangers of smoking. The present study ...aimed to examine the association of smoking with the risk of infections in a large cohort of healthy blood donors.
This cohort study used questionnaire and health register data from 127 831 Danish blood donors. Multivariable Cox proportional hazards analysis was applied to estimate the association of current smoking with the risk of all-cause infection defined as hospital-based treatment for infection or filled prescriptions of antimicrobials stratified for age and adjusted for relevant confounders.
Among 18 272 current smokers, 12 272 filled an antimicrobial prescription and 2035 received hospital-based treatment for infections. Among 101 974 non-smokers, 65 117 filled a prescription and 8501 received hospital-based treatment for infections. Smokers had a higher risk of all-cause infection than non-smokers (hazard ratio estimates were 1.27 in males and 1.33 in females for hospital-based treatment and 1.11 in males and up to 1.20 in females for filled prescriptions). Smoking was most strongly associated with an increased incidence of respiratory tract infection, abscesses, skin infection, and prescriptions for these ailments (hazard ratio up to 2.29). Furthermore, smokers' risk of filled prescriptions of broad-spectrum penicillin was increased (hazard ratio up to 1.96).
Current smoking was strongly associated with the risk of hospital-based treatment of infection and filled prescriptions of antimicrobials in a large cohort of healthy individuals. These findings warrant an increased focus on infectious disease risk among smokers.
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Purpose
Hyperhidrosis has been associated with a reduced health-related quality of life (HRQoL). The role of common confounding factors of this association such as stress and socioeconomic status, ...however, remain largely unexplored, and may affect the management strategy for hyperhidrosis. Therefore, the study objective was to compare the HRQoL in individuals with and without hyperhidrosis while adjusting for confounders.
Methods
In this retrospective cohort study, data on the HRQoL measured by the short-form-12 questionnaire and self-reported hyperhidrosis were collected from the Danish Blood Donor Study-cohort. Data on international classification of disease-10 codes and redeemed prescriptions were collected from nationwide registries. Linear regression investigated the association between hyperhidrosis and HRQoL.
Results
Total 2794 (9.1%) of 30,808 blood donors had self-reported hyperhidrosis and 284 (0.2%) of 122,225 had hospital diagnosed hyperhidrosis. Self-reported hyperhidrosis was associated with a reduced mental HRQoL (adjusted beta coefficient − 1.10; 95% confidence interval − 1.37, − 0.82;
p
< 0.001) and physical HRQoL (adjusted beta coefficient − 0.90; 95% confidence interval − 1.09, − 0.70;
p
< 0.001). Hospital diagnosed hyperhidrosis was associated with a reduced mental HRQoL (adjusted beta coefficient − 0.91; 95% confidence interval − 1.82, − 0.04;
p
= 0.049).
Conclusion
Hyperhidrosis is associated with a reduced HRQoL, independently of confounders or mode of diagnosis. This supports an approach primarily targeting hyperhidrosis.
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