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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 CI[0.79-0.93] p < .001. Compared to blood type O, the blood types B, A, and AB were found more susceptible toward infection with ORs 1.1 CI[1.06-1.14] p < .001, 1.17 CI[1.14-1.2] p < .001, and 1.2 CI[1.14-1.26] 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.
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Antígenos de Grupos Sanguíneos , COVID-19 , Síndrome de COVID-19 Pós-Aguda , Humanos , Sistema ABO de Grupos Sanguíneos , Antígenos de Grupos Sanguíneos/genética , Estudos de Coortes , COVID-19/sangue , COVID-19/genética , Síndrome de COVID-19 Pós-Aguda/sangue , Síndrome de COVID-19 Pós-Aguda/genética , SARS-CoV-2 , Predisposição Genética para DoençaRESUMO
BACKGROUND: Accurate blood type data are essential for blood bank management, but due to costs, few of 43 blood group systems are routinely determined in Danish blood banks. However, a more comprehensive dataset of blood types is useful in scenarios such as rare blood type allocation. We aimed to investigate the viability and accuracy of predicting blood types by leveraging an existing dataset of imputed genotypes for two cohorts of approximately 90,000 each (Danish Blood Donor Study and Copenhagen Biobank) and present a more comprehensive overview of blood types for our Danish donor cohort. STUDY DESIGN AND METHODS: Blood types were predicted from genome array data using known variant determinants. Prediction accuracy was confirmed by comparing with preexisting serological blood types. The Vel blood group was used to test the viability of using genetic prediction to narrow down the list of candidate donors with rare blood types. RESULTS: Predicted phenotypes showed a high balanced accuracy >99.5% in most cases: A, B, C/c, Coa /Cob , Doa /Dob , E/e, Jka /Jkb , Kna /Knb , Kpa /Kpb , M/N, S/s, Sda , Se, and Yta /Ytb , while some performed slightly worse: Fya /Fyb , K/k, Lua /Lub , and Vel ~99%-98% and CW and P1 ~96%. Genetic prediction identified 70 potential Vel negatives in our cohort, 64 of whom were confirmed correct using polymerase chain reaction (negative predictive value: 91.5%). DISCUSSION: High genetic prediction accuracy in most blood groups demonstrated the viability of generating blood types using preexisting genotype data at no cost and successfully narrowed the pool of potential individuals with the rare Vel-negative phenotype from 180,000 to 70.
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Antígenos de Grupos Sanguíneos , Humanos , Antígenos de Grupos Sanguíneos/genética , Genótipo , Fenótipo , Doadores de Sangue , Reação em Cadeia da PolimeraseRESUMO
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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Hiperidrose , Qualidade de Vida , Humanos , Morbidade , Qualidade de Vida/psicologia , Estudos Retrospectivos , Inquéritos e QuestionáriosRESUMO
BACKGROUND: Although the vast majority of individuals succumbing to infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are elderly, infection fatality rate (IFR) estimates for the age group ≥70 years are still scarce. To this end, we assessed SARS-CoV-2 seroprevalence among retired blood donors and combined it with national coronavirus disease 2019 (COVID-19) survey data to provide reliable population-based IFR estimates for this age group. METHODS: We identified 60â 926 retired blood donors aged ≥70 years in the rosters of 3 regionwide Danish blood banks and invited them to fill in a questionnaire on COVID-19-related symptoms and behaviors. Among 24â 861 (40.8%) responders, we invited a random sample of 3200 individuals for blood testing. Overall, 1201 (37.5%) individuals were tested for SARS-CoV-2 antibodies (Wantai) and compared with 1110 active blood donors aged 17-69 years. Seroprevalence 95% confidence intervals (CIs) were adjusted for assay sensitivity and specificity. RESULTS: Among retired (aged ≥70 years) and active (aged 17-69 years) blood donors, adjusted seroprevalences were 1.4% (95% CI, .3-2.5%) and 2.5% (95% CI, 1.3-3.8%), respectively. Using available population data on COVID-19-related fatalities, IFRs for patients aged ≥70 years and for 17-69 years were estimated at 5.4% (95% CI, 2.7-6.4%) and .083% (95% CI, .054-.18%), respectively. Only 52.4% of SARS-CoV-2-seropositive retired blood donors reported having been sick since the start of the pandemic. CONCLUSIONS: COVID-19 IFR in the age group >69 years is estimated to be 65 times the IFR for people aged 18-69 years.
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COVID-19 , SARS-CoV-2 , Idoso , Anticorpos Antivirais , Doadores de Sangue , Estudos Transversais , Dinamarca , Humanos , Estudos SoroepidemiológicosRESUMO
BACKGROUND: Blood donors report better health-related quality of life (HRQL) than non-donors. Likewise, donors reporting good health are less likely to stop donating and have a higher donation frequency. This is evidence of the healthy donor effect (HDE). This study is the first to investigate the impact of HRQL and depressive symptoms on subsequent donor career. STUDY DESIGN AND METHODS: Prospective cohort study includes 102,065 participants from the Danish Blood Donor Study applying the 12-item short-form health survey (SF-12) measuring a mental (MCS) and a physical component score (PCS) and the Major Depression Inventory (MDI). Poisson and Cox regression models were used to assess the effect of SF-12 and MDI scores on donation frequency and donor cessation. Higher MCS/PCS scores indicate good HRQL, while higher MDI score indicates higher experience of depressive symptoms. RESULTS: For both sexes, MCS was positively correlated with donation frequency for up to 5 years, and similarly for PCS among women. A negative correlation between MDI score and donation frequency in the year following assessment was observed only among men. No correlation was observed among women. An increase in both MCS and PCS was associated with a lower risk of donation cessation in both sexes, while an increase in MDI score was only associated with an increased risk of donation cessation in men. CONCLUSION: MCS, PCS, and MDI score affect donor career. Thus, adjusting for donation frequency may reduce HDE-bias in donor health research. However, because of the small effect sizes, other ways of quantifying HDE may be beneficial.
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Doadores de Sangue , Depressão/epidemiologia , Nível de Saúde , Qualidade de Vida , Adulto , Dinamarca , Depressão/diagnóstico , Seleção do Doador , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , AutorrelatoRESUMO
BACKGROUND: Blood donors have an increased risk of low hemoglobin (Hb) levels due to iron deficiency. Therefore, knowledge of genetic variants associated with low Hb could facilitate individualized donation intervals. We have previously reported three specific single-nucleotide polymorphisms that were associated with ferritin levels in blood donors. In this study, we investigated the effect of these single-nucleotide polymorphisms on Hb levels in 15,567 Danish blood donors. STUDY DESIGN AND METHODS: We studied 15,567 participants in the Danish Blood Donor Study. The examined genes and single-nucleotide polymorphisms were 1) TMPRSS6, involved in regulation of hepcidin: rs855791; 2) HFE, associated with hemochromatosis: rs1800562 and rs1799945; 3) BTBD9, associated with restless leg syndrome: rs9357271; and 4) TF, encoding transferrin: rs2280673 and rs1830084. Associations with Hb levels and risk of Hb deferral were assessed in multivariable linear and logistic regression models. RESULTS: The HFE,rs1800562 G-allele and the HFE rs1799945 C-allele were associated with lower Hb levels in men and women, and with an increased risk of Hb below 7.8 mmol/L (12.5 g/dL) in women. Only the rs1799945 C-allele increased the risk of Hb below 8.4 mmol/L (13.5 g/dL) in men. In TMPRSS6, the rs855791 T-allele was associated with lower Hb levels in both men and women, and with an increased risk of low Hb among women. CONCLUSION: With this study we demonstrate that HFE and TMPRSS6 are associated with Hb levels and risk of Hb below the limit of deferral. Thus, genetic testing may be useful in a future assay for personalized donation intervals.
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Doadores de Sangue , Hemoglobinas/metabolismo , Alelos , Dinamarca , Feminino , Proteína da Hemocromatose/genética , Hepcidinas/metabolismo , Humanos , Masculino , Proteínas de Membrana/genética , Serina Endopeptidases/genéticaRESUMO
BACKGROUND AND OBJECTIVES: Chronic red-cell transfusions may be an indispensable part of patient treatment and may require early intervention to avoid adverse transfusion effects. The population of chronic transfusion recipients including common diagnoses and survival remains poorly characterised. Thus, the objective was to examine the complete range of chronic transfusion recipients, including demographic and patient characteristics and survival. MATERIALS AND METHODS: All patients who received their first transfusion in Sweden or Denmark from January 1, 2002 to December 31, 2010 were followed up for subsequent transfusion episodes until December 31, 2012. Data on patient characteristics at time of the first and subsequent transfusions were retrieved from the national registers. We estimated the proportion of transfused patients who experienced 20 or more red-cell transfusion episodes (with an episode defined as all transfusions received 4 days or less apart) and characterised this patient population with respect to diagnoses, demographics and survival. RESULTS: Among 893 117 first time red-cell transfusion recipients, 6157 (0·7%) experienced 20 or more episodes in total. The most common diagnoses among these patients were haematologic malignancies followed by non-haematologic malignancies and non-malignant blood and immune system related diseases. On average, chronically transfused patients had a median survival of less than 1 year following their 20th transfusion episode. CONCLUSION: This study provides an overview of patient characteristics related to repeat red-cell transfusions and of the amount of red-cell transfusion episodes administered during a 10-year period in two countries. Patients who become chronically transfused suffer from diseases with poor prognosis.
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Transfusão de Eritrócitos/efeitos adversos , Reação Transfusional/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Pré-Escolar , Dinamarca , Transfusão de Eritrócitos/estatística & dados numéricos , Feminino , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , Suécia , Reação Transfusional/mortalidadeAssuntos
Hiperidrose , Transtornos do Sono-Vigília , Humanos , Depressão/epidemiologia , Depressão/etiologia , Doadores de Sangue , Estudos Retrospectivos , Transtornos do Sono-Vigília/epidemiologia , Transtornos do Sono-Vigília/etiologia , Fadiga/epidemiologia , Fadiga/etiologia , Hiperidrose/epidemiologia , Sono , Dinamarca/epidemiologia , Inquéritos e QuestionáriosRESUMO
BACKGROUND: The prevalence of disease-related malnutrition in Western European hospitals is estimated to be about 30%. There is no consensus whether poor nutritional status causes poorer clinical outcome or if it is merely associated with it. The intention with all forms of nutrition support is to increase uptake of essential nutrients and improve clinical outcome. Previous reviews have shown conflicting results with regard to the effects of nutrition support. OBJECTIVES: To assess the benefits and harms of nutrition support versus no intervention, treatment as usual, or placebo in hospitalised adults at nutritional risk. SEARCH METHODS: We searched Cochrane Central Register of Controlled Trials (CENTRAL) in the Cochrane Library, MEDLINE (Ovid SP), Embase (Ovid SP), LILACS (BIREME), and Science Citation Index Expanded (Web of Science). We also searched the World Health Organization International Clinical Trials Registry Platform (www.who.int/ictrp); ClinicalTrials.gov; Turning Research Into Practice (TRIP); Google Scholar; and BIOSIS, as well as relevant bibliographies of review articles and personal files. All searches are current to February 2016. SELECTION CRITERIA: We include randomised clinical trials, irrespective of publication type, publication date, and language, comparing nutrition support versus control in hospitalised adults at nutritional risk. We exclude trials assessing non-standard nutrition support. DATA COLLECTION AND ANALYSIS: We used standard methodological procedures expected by Cochrane and the Cochrane Hepato-Biliary Group. We used trial domains to assess the risks of systematic error (bias). We conducted Trial Sequential Analyses to control for the risks of random errors. We considered a P value of 0.025 or less as statistically significant. We used GRADE methodology. Our primary outcomes were all-cause mortality, serious adverse events, and health-related quality of life. MAIN RESULTS: We included 244 randomised clinical trials with 28,619 participants that met our inclusion criteria. We considered all trials to be at high risk of bias. Two trials accounted for one-third of all included participants. The included participants were heterogenous with regard to disease (20 different medical specialties). The experimental interventions were parenteral nutrition (86 trials); enteral nutrition (tube-feeding) (80 trials); oral nutrition support (55 trials); mixed experimental intervention (12 trials); general nutrition support (9 trials); and fortified food (2 trials). The control interventions were treatment as usual (122 trials); no intervention (107 trials); and placebo (15 trials). In 204/244 trials, the intervention lasted three days or more.We found no evidence of a difference between nutrition support and control for short-term mortality (end of intervention). The absolute risk was 8.3% across the control groups compared with 7.8% (7.1% to 8.5%) in the intervention groups, based on the risk ratio (RR) of 0.94 (95% confidence interval (CI) 0.86 to 1.03, P = 0.16, 21,758 participants, 114 trials, low quality of evidence). We found no evidence of a difference between nutrition support and control for long-term mortality (maximum follow-up). The absolute risk was 13.2% in the control group compared with 12.2% (11.6% to 13%) following nutritional interventions based on a RR of 0.93 (95% CI 0.88 to 0.99, P = 0.03, 23,170 participants, 127 trials, low quality of evidence). Trial Sequential Analysis showed we only had enough information to assess a risk ratio reduction of approximately 10% or more. A risk ratio reduction of 10% or more could be rejected.We found no evidence of a difference between nutrition support and control for short-term serious adverse events. The absolute risk was 9.9% in the control groups versus 9.2% (8.5% to 10%), with nutrition based on the RR of 0.93 (95% CI 0.86 to 1.01, P = 0.07, 22,087 participants, 123 trials, low quality of evidence). At long-term follow-up, the reduction in the risk of serious adverse events was 1.5%, from 15.2% in control groups to 13.8% (12.9% to 14.7%) following nutritional support (RR 0.91, 95% CI 0.85 to 0.97, P = 0.004, 23,413 participants, 137 trials, low quality of evidence). However, the Trial Sequential Analysis showed we only had enough information to assess a risk ratio reduction of approximately 10% or more. A risk ratio reduction of 10% or more could be rejected.Trial Sequential Analysis of enteral nutrition alone showed that enteral nutrition might reduce serious adverse events at maximum follow-up in people with different diseases. We could find no beneficial effect of oral nutrition support or parenteral nutrition support on all-cause mortality and serious adverse events in any subgroup.Only 16 trials assessed health-related quality of life. We performed a meta-analysis of two trials reporting EuroQoL utility score at long-term follow-up and found very low quality of evidence for effects of nutritional support on quality of life (mean difference (MD) -0.01, 95% CI -0.03 to 0.01; 3961 participants, two trials). Trial Sequential Analyses showed that we did not have enough information to confirm or reject clinically relevant intervention effects on quality of life.Nutrition support may increase weight at short-term follow-up (MD 1.32 kg, 95% CI 0.65 to 2.00, 5445 participants, 68 trials, very low quality of evidence). AUTHORS' CONCLUSIONS: There is low-quality evidence for the effects of nutrition support on mortality and serious adverse events. Based on the results of our review, it does not appear to lead to a risk ratio reduction of approximately 10% or more in either all-cause mortality or serious adverse events at short-term and long-term follow-up.There is very low-quality evidence for an increase in weight with nutrition support at the end of treatment in hospitalised adults determined to be at nutritional risk. The effects of nutrition support on all remaining outcomes are unclear.Despite the clinically heterogenous population and the high risk of bias of all included trials, our analyses showed limited signs of statistical heterogeneity. Further trials may be warranted, assessing enteral nutrition (tube-feeding) for different patient groups. Future trials ought to be conducted with low risks of systematic errors and low risks of random errors, and they also ought to assess health-related quality of life.
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Alimentos Fortificados , Desnutrição/prevenção & controle , Apoio Nutricional , Adulto , Peso Corporal , Causas de Morte , Nutrição Enteral/efeitos adversos , Nutrição Enteral/estatística & dados numéricos , Alimentos Fortificados/estatística & dados numéricos , Hospitalização , Humanos , Desnutrição/mortalidade , Apoio Nutricional/efeitos adversos , Apoio Nutricional/estatística & dados numéricos , Nutrição Parenteral/efeitos adversos , Nutrição Parenteral/estatística & dados numéricos , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
PURPOSE: Systemizer Profile Questionnaire (SPQ), which has not been used before, investigates difficulties in mentalisation, sensory- and/or social sensitivity and social cognition (MSSSC) in subjects with Autism-Spectrum-Disorders (ASD) with and without Attention-Deficit-Hyperactivity-Disorder (ADHD). The aim of this study was to evaluate the reliability and validity of the SPQ domains, and to assess the predictive validity of the SPQ against the Ritvo Autism Asperger Diagnostic Scale (RAADS). METHODS: Three-hundred-fifty-four study subjects with ICD-10 verified ASD confirmed by RAADS and 354 controls matched on age group and gender were recruited and evaluated systematically with SPQ, standardized questions about demographic and clinical data. Hypothesized SPQ subscales formed from 85 items were evaluated using confirmatory factor analysis (CFA). Resulting revised sub-scales were confirmed using item response theory (IRT) and the predictive validity of the SPQ scores was evaluated using RAADS scores above 64 as the standard. RESULTS: Twenty-two of the original 85 items were removed, resulting in an instrument with 63 items across nine psychometrically valid domains. These domains had high sensitivity (range: 0.64 to 0.84), and high specificity (range: 0.73 to 0.90). Positive predictive values (range: 0.76 to 0.89) and negative predictive values (range: 0.69 to 0.90) were also high. For the total SPQ score the sensitivity was 0.95, the specificity was 0.87, the positive predictive value was 0.88 and the negative predictive value was 0.95. CONCLUSION: SPQ domains are valid descriptions/profiles of MSSSC given that ASD is confirmed by RAADS, though irrelevant if not, as SPQ is not a diagnostic instrument.
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Headache disorders are the most common disorders of the nervous system. The lifetime prevalence of headache disorders show that some individuals never experience headache. The etiology of complete freedom from headache is not known. To assess genetic variants associated with complete freedom from headache, we performed a genome-wide association study of individuals who have never experienced a headache. We included 63,992 individuals (2,998 individuals with complete freedom from headache and 60,994 controls) from the Danish Blood Donor Study Genomic Cohort. Participants were included in two rounds, from 2015 to 2018 and in 2020. We discovered a genome-wide significant association, with the lead variant rs7904615[G] in ADARB2 (EAF = 27%, OR = 1.20 [1.13-1.27], p = 3.92 × 10-9). The genomic locus was replicated in a non-overlapping cohort of 13,032 individuals (539 individuals with complete freedom from headache and 12,493 controls) from the Danish Blood Donor Study Genomic Cohort (p < 0.05, two-sided). Participants for the replication were included from 2015 to 2020. In conclusion, we show that complete freedom from headache has a genetic component, and we suggest that ADARB2 is involved in complete freedom from headache. The genomic locus was specific for complete freedom from headache and was not associated with any primary headache disorders.
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Doadores de Sangue , Estudo de Associação Genômica Ampla , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos de Coortes , Dinamarca/epidemiologia , Loci Gênicos , Predisposição Genética para Doença , Cefaleia/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genéticaRESUMO
Social trust is a heritable trait that has been linked with physical health and longevity. In this study, we performed genome-wide association studies of self-reported social trust in n = 33,882 Danish blood donors. We observed genome-wide and local evidence of genetic similarity with other brain-related phenotypes and estimated the single nucleotide polymorphism-based heritability of trust to be 6% (95% confidence interval = (2.1, 9.9)). In our discovery cohort (n = 25,819), we identified one significantly associated locus (lead variant: rs12776883) in an intronic enhancer region of PLPP4, a gene highly expressed in brain, kidneys, and testes. However, we could not replicate the signal in an independent set of donors who were phenotyped a year later (n = 8063). In the subsequent meta-analysis, we found a second significantly associated variant (rs71543507) in an intergenic enhancer region. Overall, our work confirms that social trust is heritable, and provides an initial look into the genetic factors that influence it.
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Doadores de Sangue , Estudo de Associação Genômica Ampla , Humanos , Confiança , Fenótipo , Dinamarca , Polimorfismo de Nucleotídeo Único , Predisposição Genética para DoençaRESUMO
Essential tremor (ET) is a prevalent neurological disorder with a largely unknown underlying biology. In this genome-wide association study meta-analysis, comprising 16,480 ET cases and 1,936,173 controls from seven datasets, we identify 12 sequence variants at 11 loci. Evaluating mRNA expression, splicing, plasma protein levels, and coding effects, we highlight seven putative causal genes at these loci, including CA3 and CPLX1. CA3 encodes Carbonic Anhydrase III and carbonic anhydrase inhibitors have been shown to decrease tremors. CPLX1, encoding Complexin-1, regulates neurotransmitter release. Through gene-set enrichment analysis, we identify a significant association with specific cell types, including dopaminergic and GABAergic neurons, as well as biological processes like Rho GTPase signaling. Genetic correlation analyses reveals a positive association between ET and Parkinson's disease, depression, and anxiety-related phenotypes. This research uncovers risk loci, enhancing our knowledge of the complex genetics of this common but poorly understood disorder, and highlights CA3 and CPLX1 as potential therapeutic targets.
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Tremor Essencial , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Tremor Essencial/genética , Humanos , Polimorfismo de Nucleotídeo Único , Loci GênicosRESUMO
Restless legs syndrome (RLS) affects up to 10% of older adults. Their healthcare is impeded by delayed diagnosis and insufficient treatment. To advance disease prediction and find new entry points for therapy, we performed meta-analyses of genome-wide association studies in 116,647 individuals with RLS (cases) and 1,546,466 controls of European ancestry. The pooled analysis increased the number of risk loci eightfold to 164, including three on chromosome X. Sex-specific meta-analyses revealed largely overlapping genetic predispositions of the sexes (rg = 0.96). Locus annotation prioritized druggable genes such as glutamate receptors 1 and 4, and Mendelian randomization indicated RLS as a causal risk factor for diabetes. Machine learning approaches combining genetic and nongenetic information performed best in risk prediction (area under the curve (AUC) = 0.82-0.91). In summary, we identified targets for drug development and repurposing, prioritized potential causal relationships between RLS and relevant comorbidities and risk factors for follow-up and provided evidence that nonlinear interactions are likely relevant to RLS risk prediction.
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Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Síndrome das Pernas Inquietas , Síndrome das Pernas Inquietas/genética , Humanos , Fatores de Risco , Feminino , Masculino , Polimorfismo de Nucleotídeo Único , Análise da Randomização Mendeliana , Aprendizado de MáquinaRESUMO
BACKGROUND: The emerging use of biomarkers in research and tailored care introduces a need for information about the association between biomarkers and basic demographics and lifestyle factors revealing expectable concentrations in healthy individuals while considering general demographic differences. METHODS: A selection of 47 biomarkers, including markers of inflammation and vascular stress, were measured in plasma samples from 9876 Danish Blood Donor Study participants. Using regression models, we examined the association between biomarkers and sex, age, Body Mass Index (BMI), and smoking. RESULTS: Here we show that concentrations of inflammation and vascular stress biomarkers generally increase with higher age, BMI, and smoking. Sex-specific effects are observed for multiple biomarkers. CONCLUSION: This study provides comprehensive information on concentrations of 47 plasma biomarkers in healthy individuals. The study emphasizes that knowledge about biomarker concentrations in healthy individuals is critical for improved understanding of disease pathology and for tailored care and decision support tools.
Blood-based biomarkers are circulating molecules that can help to indicate health or disease. Biomarker levels may vary depending on demographic and lifestyle factors such as age, sex, smoking status, and body mass index. Here, we examine the effects of these demographic and lifestyle factors on levels of biomarkers related to activation of the immune system and cardiovascular stress. Measurements of 47 different proteins were performed on blood samples from nearly 10,000 healthy Danish blood donors. Measurement data were linked with questionnaire data to assess effects of lifestyle. We found that immune activation and vascular stress generally increased with age, BMI, and smoking. As these measurements are from healthy blood donors they can serve as a reference for expectable effects and inflammation levels in healthy individuals. Knowledge about the healthy state is important for understanding disease progression and optimizing care.
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Introduction: Antigen presentation and antimicrobial immune responses involve the human leukocyte antigen (HLA) system. Onychomycosis is primarily caused by dermatophytes and affects around 5.5% of the population worldwide. Yet, only limited data exist on the associations between the HLA system and onychomycosis. Thus, the objective of the study was to investigate if there is an association between HLA alleles and onychomycosis. Methods: Participants in the Danish Blood Donor Study were defined as cases of onychomycosis and controls based on antifungal prescriptions in the national prescription registry. Associations were investigated using logistic regressions adjusted for confounders and were Bonferroni corrected for multiple tests. Results: A total of 3,665 participants were considered onychomycosis cases, and 24,144 participants were considered controls. We found two protective HLA alleles of onychomycosis: DQB1*06:04, odds ratios (OR) 0.80 (95% confidence interval (CI) 0.71-0.90), and DRB1*13:02, OR 0.79 (95% CI: 0.71-0.89). Conclusion: The finding of two novel protective alleles of onychomycosis indicates that certain HLA alleles have certain antigen presentation properties affecting the risk of fungal infection. These findings may provide the basis for future research identifying immunologically relevant antigens of fungi causing onychomycosis, which could ultimately lead to targets of new drugs with antifungal effects.
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Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease associated with psychiatric comorbidity. Attention deficit hyperactivity disorder (ADHD) is a mental disorder associated with systemic and skin inflammation such as psoriasis and atopic dermatitis. Whether HS symptoms are associated with ADHD symptoms remains unexplored. Thus, the aim of this study was to explore the possible association between HS and ADHD. Participants in the Danish Blood Donor Study (DBDS) were included in this cross-sectional study during 2015-2017. The participants provided questionnaire data on screening items of HS, ADHD symptoms (ASRS-score), and depressive symptoms, smoking and body mass index (BMI). A logistic regression with HS symptoms as a binary outcome predicted by ADHD adjusted for age, sex, smoking, BMI, and depression was conducted to investigate the association between HS and ADHD. A total of 52,909 Danish blood donors were included in the study. Of these were 1004/52,909 (1.9%) considered participants with HS. Of the participants with HS, 74/996 (7.4%) screened positive of ADHD symptoms, while only 1786/51,129 (3.5%) of the participants without HS screened positive of ADHD. Adjusted for confounders, ADHD was positively associated with HS, odds ratio 1.85 (95% confidence interval: 1.43-2.37). Psychiatric comorbidity of HS is not limited to depression and anxiety. This study shows a positive association between HS and ADHD. Further research on the biological mechanisms behind this association is warranted.
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Importance: There is a need for better recognition and more extensive research into menstrual migraine (MM) in the general population, and a revision of the diagnostic criteria for MM is warranted to move the field forward. Increased understanding of MM is crucial for improving clinical care, diagnosis, and therapy for MM. Objectives: To assess the clinical characteristics of MM, including severity and treatment response, and to propose new diagnostic criteria for pure MM and menstrually related migraine. Design, Setting, and Participants: This is a case-control study of Danish individuals with migraine. All individuals completed a 105-item validated diagnostic migraine questionnaire, sent via the Danish electronic mailing system (e-Boks) between May and August 2020, allowing diagnosis of pure MM and menstrually related migraine by the International Classification of Headache Disorders, Third Edition (ICHD-3). Data analysis was performed from September 2021 to November 2022. Exposure: Diagnosis of migraine. Main Outcomes and Measures: Clinical characteristics of women with MM and women with nonmenstrual migraine (non-MM) were compared using the ICHD-3 diagnostic criteria. A simulation of the risk of randomly misclassifying MM was based on number of migraine attacks during 3 menstrual cycles (3 × 28 days), and simulation analyses were performed using 100â¯000 permutations of random migraine attacks in migraine patients. Results: A total of 12â¯618 individuals, including 9184 women, with migraine participated in the study. Among the women with migraine, the prevalence of MM was 16.6% (1532 women), and the prevalence of non-MM was 45.9% (4216 women). The mean (SD) age was 38.7 (8.7) years for women with MM and 37.0 (9.2) years for women with non-MM. Of the 1532 women with MM, 410 (26.8%) fulfilled ICHD-3 diagnostic criteria for pure MM, 1037 (67.7%) fulfilled ICHD-3 diagnostic criteria for menstrually related migraine, and 152 (9.9%) fulfilled proposed diagnostic criteria for rare pure MM. MM was associated with a higher frequency of migraine-accompanying symptoms (odds ratio [OR], 1.98; 95% CI, 1.71-2.29), more frequent (OR, 7.21; 95% CI, 5.77-9.03) and more severe (OR, 1.17; 95% CI, 1.13-1.21) migraine attacks, lower frequency of nonmigraine headache (OR, 0.31; 95% CI, 0.18-0.49), an overall greater response to treatment with triptans (OR, 1.66; 95% CI, 1.24-2.24), better improvement of migraine attacks during late pregnancy (OR, 5.10; 95% CI, 2.17-14.00), and faster reappearance of migraine attacks post partum (OR, 3.19; 95% CI, 2.40-4.25). Hormonal contraceptive-related MM was associated with a higher prevalence of migraine without aura than migraine related to spontaneous menstruation (OR, 1.82; 95% CI, 1.62-2.06). Otherwise, no differences between hormonal and spontaneous MM were observed. The risk of random diagnostic misclassification of ICHD-3 menstrually related migraine in women with high frequency episodic migraine was 43%. This risk was reduced to 3% when applying the proposed criteria for menstrually related migraine. Conclusions and Relevance: In this case-control study, MM in the general population had clinical characteristics that were quantitively different from those of non-MM. Detailed descriptive data and suggested improved diagnostic criteria for pure MM and menstrually related migraine were provided.
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Transtornos de Enxaqueca , Humanos , Feminino , Gravidez , Adulto , Estudos de Casos e Controles , Transtornos de Enxaqueca/diagnóstico , Transtornos de Enxaqueca/epidemiologia , Transtornos de Enxaqueca/tratamento farmacológico , Cefaleia/epidemiologia , Menstruação , Ciclo Menstrual/fisiologiaRESUMO
OBJECTIVES: To examine the level of loneliness experienced during the COVID-19 pandemic in Denmark and to identify associated behavioural patterns and demographic factors. DESIGN: Cross-sectional cohort study. SETTING: Includes Danish active and former blood donors. PARTICIPANTS: A 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 MEASURES: Subjective 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. RESULTS: The 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. CONCLUSIONS: The 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.
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COVID-19 , Solidão , Masculino , Humanos , Adulto , Feminino , Solidão/psicologia , COVID-19/epidemiologia , Estudos Transversais , Pandemias , Depressão/psicologiaRESUMO
Background: Although the persistence of physical symptoms after SARS-CoV-2 infection is a major public health concern, evidence from large observational studies beyond one year post diagnosis remain scarce. We aimed to assess the prevalence of physical symptoms in relation to acute illness severity up to more than 2-years after diagnosis of COVID-19. Methods: This multinational study included 64,880 adult participants from Iceland, Sweden, Denmark, and Norway with self-reported data on COVID-19 and physical symptoms from April 2020 to August 2022. We compared the prevalence of 15 physical symptoms, measured by the Patient Health Questionnaire (PHQ-15), among individuals with or without a confirmed COVID-19 diagnosis, by acute illness severity, and by time since diagnosis. We additionally assessed the change in symptoms in a subset of Swedish adults with repeated measures, before and after COVID-19 diagnosis. Findings: During up to 27 months of follow-up, 34.5% participants (22,382/64,880) were diagnosed with COVID-19. Individuals who were diagnosed with COVID-19, compared to those not diagnosed, had an overall 37% higher prevalence of severe physical symptom burden (PHQ-15 score ≥15, adjusted prevalence ratio [PR] 1.37 [95% confidence interval [CI] 1.23-1.52]). The prevalence was associated with acute COVID-19 severity: individuals bedridden for seven days or longer presented with the highest prevalence (PR 2.25 [1.85-2.74]), while individuals never bedridden presented with similar prevalence as individuals not diagnosed with COVID-19 (PR 0.92 [0.68-1.24]). The prevalence was statistically significantly elevated among individuals diagnosed with COVID-19 for eight of the fifteen measured symptoms: shortness of breath, chest pain, dizziness, heart racing, headaches, low energy/fatigue, trouble sleeping, and back pain. The analysis of repeated measurements rendered similar results as the main analysis. Interpretation: These data suggest an elevated prevalence of some, but not all, physical symptoms during up to more than 2 years after diagnosis of COVID-19, particularly among individuals suffering a severe acute illness, highlighting the importance of continued monitoring and alleviation of these targeted core symptoms. Funding: This work was mainly supported by grants from NordForsk (COVIDMENT, grant number 105668 and 138929) and Horizon 2020 (CoMorMent, 847776). See Acknowledgements for further details on funding.