Mortality and risk of diabetes, liver disease, and heart disease in individuals with haemochromatosis C282Y homozygosity and normal concentrations of iron, transferrin saturation, or ferritin: prospective cohort study.

Objectives: To test whether haemochromatosis C282Y homozygotes have increased risk of diabetes, liver disease, and heart disease even when they have normal plasma iron, transferrin saturation, or ferritin concentrations and to test whether C282Y homozygotes with diabetes, liver disease, or heart disease have increased mortality compared with non-carriers with these diseases.

Design: Prospective cohort study.

Setting: Three Danish general population cohorts: the Copenhagen City Heart Study, the Copenhagen General Population Study, and the Danish General Suburban Population Study.

Normative data on measures of cardiovascular autonomic neuropathy and the effect of pretest conditions in a large Danish non-diabetic CVD-free population from the Lolland-Falster Health Study.

Purpose: Cardiovascular autonomic neuropathy (CAN) is a common diabetic complication associated with excess morbidity and mortality. CAN is also seen in conditions such as Parkinson's disease. Normative reference data for cardiovascular autonomic function are used to stratify individuals into those with and without CAN.

Thyroid Function, Diabetes, and Common Age-Related Eye Diseases: A Mendelian Randomization Study.

Previous Mendelian randomization (MR) studies showed an association between hypothyroidism and cataract and between high-normal free thyroxine (FT4) and late age-related macular degeneration (AMD), but not between FT4, thyroid stimulating hormone (TSH), or hyperthyroidism and diabetic retinopathy or cataract. These studies included a limited number of genetic variants for thyroid function and did not investigate autoimmune thyroid disease (AITD) or glaucoma, include bidirectional and multivariable MR (MVMR), and examine sex differences or potential mediation effects of diabetes. We aimed to address this knowledge gap.

The CALR mutations enhance the expression of the immunosuppressive proteins GARP and LAP on peripheral blood lymphocytes through increased binding of activated platelets.

Recently, an antibody which inhibits the glycoprotein A repetitions predominant (GARP)-mediated release of active transforming growth factor beta (TGFβ) from the TGFβ propeptide latency-associated peptide (LAP) showed preclinical activity in a murine model of the chronic myeloproliferative neoplasms (MPN). Consequently, we investigated the expression of the immunosuppressive molecules LAP and GARP on peripheral blood lymphocytes from 56 MPN patients and 11 healthy donors (HD). We found that lymphocytes from patients with MPN express higher levels of LAP and GARP with no strong differences found between the different MPN diagnoses.

Cardiorespiratory fitness, body composition, diabetes, and longevity: a two-sample Mendelian randomization study.

Context: Cardiorespiratory fitness, commonly assessed as maximal volume of oxygen consumption (VO2max), has emerged as an important predictor of morbidity and mortality.

Objective: We investigated the causality and directionality of the associations of VO2max with body composition, physical activity, diabetes, performance enhancers, and longevity.

Methods: Using publicly available summary statistics from the largest genome-wide association studies publicly available, we conducted a bidirectional two-sample Mendelian randomization (MR) study.

Iron, hemochromatosis genotypes, and risk of infections: a cohort study of 142 188 general population individuals.

It is unclear whether risk of infection is increased in individuals with hereditary hemochromatosis and in individuals with low or high plasma iron, transferrin saturation, or ferritin. Therefore, we tested whether high and low iron, transferrin saturation, and ferritin are associated with risk of infections observationally and genetically through HFE genotypes. We studied 142 188 Danish general population individuals.

Thyroid dysfunction and exudative age-related macular degeneration - A longitudinal nationwide registry-based cohort study.

Purpose: The association between thyroid dysfunction and exudative age-related macular degeneration (AMD) is unknown.

Methods: In this Danish longitudinal nationwide registry-based cohort study we included all Danish residents aged 50-100 between 2008 and 2018. Using the Danish national registries, we studied the association between thyroid dysfunction and exudative AMD.

Electrocardiographic markers in patients with type 2 diabetes and the role of diabetes duration.

Background: The association between type 2 diabetes and electrocardiographic (ECG) markers are incompletely explored and the dependence on diabetes duration is largely unknown. We aimed to investigate the electrocardiographic (ECG) changes associated with type 2 diabetes over time.

Methods: In this cross-sectional study, we matched people with type 2 diabetes 1:1 on sex, age, and body mass index with people without diabetes from the general population.

Systemic glucocorticoid exposure and postoperative infection risk in 143,782 appendectomy patients-a Danish longitudinal nationwide study.

Background: Glucocorticoids are conventionally associated with increased postoperative infection risk. It is necessary to clarify if preoperative glucocorticoid exposure is associated with postoperative infection in appendectomy patients and if the association is different for open and laparoscopic appendectomies.

Methods: A Danish nationwide study of appendectomy patients between 1996 and 2018.

Self-Reported Health as Predictor of Allostatic Load and All-Cause Mortality: Findings From the Lolland-Falster Health Study.

The aim was to determine the association between self-reported health (SRH), allostatic load (AL) and mortality. Data derived from the Lolland-Falster Health Study undertaken in Denmark from 2016-2020 ( = 14,104). Median follow-up time for death was 4.

The role of thyroid function in borderline personality disorder and schizophrenia: a Mendelian Randomisation study.

Background: Genome-wide association studies have reported a genetic overlap between borderline personality disorder (BPD) and schizophrenia (SCZ). Epidemiologically, the direction and causality of the association between thyroid function and risk of BPD and SCZ are unclear. We aim to test whether genetically predicted variations in TSH and FT4 levels or hypothyroidism are associated with the risk of BPD and SCZ.

Correlation between allostatic load index and cumulative mortality: a register-based study of Danish municipalities.

Objectives: The aim of this study was to examine population-based allostatic load (AL) indices as an indicator of community health across 14 municipalities in Denmark.

Design: Register-based study.

Setting: Data derived from: the Lolland-Falster Health Study, the Copenhagen General Population Study and the Danish General Suburban Population Study.

Neutrophil-to-lymphocyte ratio and all-cause mortality with and without myeloproliferative neoplasms-a Danish longitudinal study.

The neutrophil-to-lymphocyte ratio(NLR) is increased in chronic inflammation and myeloproliferative neoplasms (MPN). We hypothesize that NLR is associated with all-cause mortality and mortality by comorbidity burden in the general population and individuals with MPN. We included 835,430 individuals from The Danish General Suburban Population Study, general practitioners, and outpatient clinics.

JAK2V617F drives gut microbiota differences in patients with myeloproliferative neoplasms.

Background: Essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (MF) are myeloproliferative neoplasms (MPN). Inflammation is involved in the initiation, progression, and symptomology of the diseases. The gut microbiota impacts the immune system, infection control, and steady-state hematopoiesis.

Association of DIO2 and MCT10 Polymorphisms With Persistent Symptoms in LT4-Treated Patients in the UK Biobank.

Context: Some evidence suggests gene-treatment interactions might cause persistent symptoms in individuals receiving levothyroxine (LT4) treatment.

Objective: We investigated, as previously hypothesized, if single-nucleotide variations (SNVs; formerly single-nucleotide polymorphisms) in rs225014 (Thr92Ala), rs225015, or rs12885300 (ORFa-Gly3Asp) in the deiodinase 2 gene (DIO2), or rs17606253 in the monocarboxylate transporter 10 gene (MCT10) were associated with outcomes indicative of local tissue hypothyroidism in LT4-treated patients and controls.

Methods: We included 18 761 LT4-treated patients and 360 534 controls in a population-based cross-sectional study in the UK Biobank.

Pronounced gut microbiota signatures in patients with positive essential thrombocythemia.

Essential thrombocythemia (ET) is part of the Philadelphia chromosome-negative myeloproliferative neoplasms. It is characterized by an increased risk of thromboembolic events and also to a certain degree hypermetabolic symptoms. The gut microbiota is an important initiator of hematopoiesis and regulation of the immune system, but in patients with ET, where inflammation is a hallmark of the disease, it is vastly unexplored.

Whole blood transcriptional profiling reveals highly deregulated atherosclerosis genes in Philadelphia-chromosome negative myeloproliferative neoplasms.

Background: The Philadelphia-negative chronic myeloproliferative neoplasms (MPNs) are associated with a huge comorbidity burden, including an increased risk of cardiovascular diseases. Recently, chronic inflammation has been suggested to be the driving force for clonal evolution and disease progression in MPN but also potentially having an impact upon the development of accelerated (premature) atherosclerosis.

Objectives: Since chronic inflammation, atherosclerosis, and atherothrombosis are prevalent in MPNs and we have previously shown oxidative stress genes to be markedly upregulated in MPNs, we hypothesized that genes linked to development of atherosclerosis might be highly deregulated as well.

JAK2V617F mutation is highly prevalent in patients with ischemic stroke: a case-control study.

Ischemic stroke has a high recurrence rate despite treatment. This underlines the significance of investigating new possible cerebrovascular risk factors, such as the acquired gene mutation JAK2V617F found in 3.1% of the general population.

High JAK2V617F variant allele frequency is associated with coronary artery but not aortic valve calcifications in patients with Philadelphia-negative myeloproliferative neoplasms.

Background: Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs) have a higher burden of cardiac calcifications compared to the general population. It is not known whether the JAK2V617F mutation is associated with increased cardiac calcification.

Aim: To investigate if a higher JAK2V617F variant allele frequency (VAF) is associated with severe coronary atherosclerosis and the presence of aortic valve calcification (AVC).