VLDL triglycerides and cholesterol in non-alcoholic fatty liver disease and myocardial infarction.

Background And Aims: Myocardial infarction is a leading cause of death in individuals with non-alcoholic fatty liver disease (NAFLD). The two diseases share elevated very low-density lipoproteins (VLDL) carrying both triglycerides and cholesterol; however, in NAFLD mainly triglycerides accumulate in liver cells while in myocardial infarction mainly cholesterol accumulates in the atherosclerotic plaque. We hypothesized that VLDL triglycerides preferentially associate with risk of NAFLD, while VLDL cholesterol preferentially associates with risk of myocardial infarction.

High fat in blood and body and increased risk of clinically diagnosed non-alcoholic fatty liver disease in 105,981 individuals.

Background And Aims: High caloric diets rich in fat and carbohydrates lead to increased fat accumulation in adipose tissue and blood. This may lead to increased risk of non-alcoholic fatty liver disease. We hypothesized that baseline high nonfasting plasma triglycerides, body mass index (BMI), and waist circumference, individually and combined, associate with increased risk of clinically diagnosed non-alcoholic fatty liver disease during follow-up.

Lipoprotein(a) during COVID-19 hospitalization: Thrombosis, inflammation, and mortality.

Background And Aims: High levels of lipoprotein(a) could worsen the outcome of COVID-19 due to prothrombotic and proinflammatory properties of lipoprotein(a). We tested the hypotheses that during COVID-19 hospitalization i) increased thrombotic activity and inflammation are associated with lipoprotein(a) levels, and ii) lipoprotein(a) levels are associated with rate of hospital death and discharge.

Methods: We studied 211 patients admitted to Copenhagen University Hospital in 2020 with COVID-19, that is, prior to any vaccination.

New insights into the genetic etiology of Alzheimer's disease and related dementias.

Characterization of the genetic landscape of Alzheimer's disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/'proxy' AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis.

Asthma and COPD versus phenotypic traits: Toward precision medicine in chronic airway disease.

Background: Asthma and COPD diagnoses are used to classify chronic airway diseases; however, both diseases are related to phenotypic traits like allergy, obesity, cough, sputum production, low-grade inflammation, smoking, elevated blood eosinophil count, comorbidities, and occupational exposures. Whether such traits can replace asthma and COPD diagnoses when assessing risk of exacerbation is unclear. We tested the hypothesis that individuals with either asthma or COPD diagnoses have similar risk of moderate and severe exacerbations when adjusted for differences in phenotypic traits.

Discovery of rare variants associated with blood pressure regulation through meta-analysis of 1.3 million individuals.

Genetic studies of blood pressure (BP) to date have mainly analyzed common variants (minor allele frequency > 0.05). In a meta-analysis of up to ~1.

Dickkopf-1 Overexpression in vitro Nominates Candidate Blood Biomarkers Relating to Alzheimer's Disease Pathology.

Background: Previous studies suggest that Dickkopf-1 (DKK1), an inhibitor of Wnt signaling, plays a role in amyloid-induced toxicity and hence Alzheimer's disease (AD). However, the effect of DKK1 expression on protein expression, and whether such proteins are altered in disease, is unknown.

Objective: We aim to test whether DKK1 induced protein signature obtained in vitro were associated with markers of AD pathology as used in the amyloid/tau/neurodegeneration (ATN) framework as well as with clinical outcomes.

Meta-analysis of up to 622,409 individuals identifies 40 novel smoking behaviour associated genetic loci.

Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants).

Identification and Replication of Six Loci Associated With Gallstone Disease.

Gallstone disease is a common complex disease that confers a substantial economic burden on society. The genetic underpinnings of gallstone disease remain incompletely understood. We aimed to identify genetic associations with gallstone disease using publicly available data from the UK Biobank and two large Danish cohorts.

An updated Alzheimer hypothesis: Complement C3 and risk of Alzheimer's disease-A cohort study of 95,442 individuals.

Introduction: We tested the hypothesis that low plasma complement C3 is observationally and genetically associated with high risk of Alzheimer's disease (AD).

Methods: We studied 95,442 individuals enrolled in the Copenhagen General Population Study. In genetic analyses, we further included 8367 individuals from the Copenhagen City Heart Study.

Complement C3 and Risk of Diabetic Microvascular Disease: A Cohort Study of 95202 Individuals from the General Population.

Background: Whether the complement system is involved in the development of diabetic microvascular disease is unknown. We tested the hypothesis that high concentrations of complement C3 are associated with increased risk of diabetic retinopathy, nephropathy, and neuropathy in individuals from the general population.

Methods: We studied 95202 individuals from the general population with baseline measurements of complement C3, genotyped for rs1065489, rs429608, and rs448260 determining concentrations of complement C3, and enrolled in the Copenhagen General Population Study from 2003 through 2013, following them until April 10, 2013.

Association of Blood Eosinophil and Blood Neutrophil Counts with Asthma Exacerbations in the Copenhagen General Population Study.

Background: Blood eosinophil count is a marker of eosinophilic airway inflammation and disease severity in asthma. However, blood neutrophil count might also be associated with disease severity. We tested the hypothesis that high blood eosinophil and neutrophil counts are both associated with the risk of asthma exacerbations among individuals with asthma from the general population.

Trans-ancestry meta-analyses identify rare and common variants associated with blood pressure and hypertension.

High blood pressure is a major risk factor for cardiovascular disease and premature death. However, there is limited knowledge on specific causal genes and pathways. To better understand the genetics of blood pressure, we genotyped 242,296 rare, low-frequency and common genetic variants in up to 192,763 individuals and used ∼155,063 samples for independent replication.

Negative statin-related news stories decrease statin persistence and increase myocardial infarction and cardiovascular mortality: a nationwide prospective cohort study.

Aim: We tested the hypothesis that statin-related news stories, cardiovascular disease, diabetes, statin dose, calendar year, and socio-demographic status are associated with early statin discontinuation. We also examined frequency and consequences of early statin discontinuation.

Methods And Results: From the entire Danish population, we studied 674 900 individuals aged 40 or older who were initiated on statin therapy in 1995-2010, and followed them until 31 December 2011.

Causal and synthetic associations of variants in the SERPINA gene cluster with alpha1-antitrypsin serum levels.

Several infrequent genetic polymorphisms in the SERPINA1 gene are known to substantially reduce concentration of alpha1-antitrypsin (AAT) in the blood. Since low AAT serum levels fail to protect pulmonary tissue from enzymatic degradation, these polymorphisms also increase the risk for early onset chronic obstructive pulmonary disease (COPD). The role of more common SERPINA1 single nucleotide polymorphisms (SNPs) in respiratory health remains poorly understood.

Elevated C-reactive protein levels, psychological distress, and depression in 73, 131 individuals.

CONTEXT The pathogenesis of depression is not fully understood, but studies suggest that low-grade systemic inflammation contributes to the development of depression. OBJECTIVE To test whether elevated plasma levels of C-reactive protein (CRP) are associated with psychological distress and depression. DESIGN We performed cross-sectional and prospective analyses of CRP levels in 4 clinically relevant categories using data from 2 general population studies.