Risk Stratification for Cardiovascular Disease: A Comparative Analysis of Cluster Analysis and Traditional Prediction Models.

Aim: Primary prevention of cardiovascular disease (CVD) relies on effective risk stratification to guide interventions. Current models, primarily developed using regression analysis, can lead to inaccurate estimates when applied to external populations. This study evaluates the utility of cluster analysis as an alternative method for developing CVD risk stratification models, comparing its performance with established CVD risk prediction models.

Health-related quality of life in surgically treated asymptomatic meningioma patients: A population-based matched cohort study.

Background: Asymptomatic patients with meningiomas are increasingly detected, where management can be challenging in terms of surgery versus watchful waiting. Health-related quality of life (HRQoL) is an important factor in clinical decision-making, albeit not greatly studied in this patient group. The aim of this paper is to map the HRQoL among patients with surgically removed asymptomatic meningioma as compared to the general population.

Predicting new cases of hypertension in Swedish primary care with a machine learning tool.

Background: Many individuals with hypertension remain undiagnosed. We aimed to develop a predictive model for hypertension using diagnostic codes from prevailing electronic medical records in Swedish primary care.

Methods: This sex- and age-matched case-control (1:5) study included patients aged 30-65 years living in the Stockholm Region, Sweden, with a newly recorded diagnosis of hypertension during 2010-19 (cases) and individuals without a recorded hypertension diagnosis during 2010-19 (controls), in total 507,618 individuals.

The influence of the COVID-19 pandemic on physical activity in Stockholm County - Evidence from time series models of smartphone measured daily steps data spanning over 3 years.

Background: It has been reported that physical activity levels decreased during the COVID-19 pandemic. Previous studies often relied on self-reported physical activity, which has low accuracy. Studies based on objectively measured physical activity have had short data collection periods, thereby not allowing the consideration of pre-pandemic levels of physical activity or the influence over the different waves of the pandemic.

Undiagnosed type 2 diabetes is common - intensified screening of established risk groups is imperative in Sweden: the SDPP cohort.

Background: Undiagnosed type 2 diabetes (T2D) is a global problem. Current strategies for diagnosis in Sweden include screening individuals within primary healthcare who are of high risk, such as those with hypertension, obesity, prediabetes, family history of diabetes, or those who smoke daily. In this study, we aimed to estimate the proportion of individuals with undiagnosed T2D in Stockholm County and factors associated with T2D being diagnosed by healthcare.

Mode of delivery and subsequent self-perceived sexual life satisfaction: a population-based cohort study.

Background: The potential association between mode of obstetrical delivery and subsequent sexual outcomes of the birthing parent remains uncertain and has not been well investigated from the perspective of positive sexual life satisfaction.

Objective: This study aimed to investigate if there was any association between mode of delivery and subsequent sexual life satisfaction of the birthing parent. A secondary aim was to assess the extent to which this association changed when stratified by time elapsed since delivery.

Migration background, eating disorder symptoms and healthcare service utilisation: findings from the Stockholm Public Health Cohort.

Background: From a global perspective, eating disorders are increasingly common, probably because of societal transformation and improved detection. However, research on the impact of migration on the development of eating disorders is scarce, and previously reported results are conflicting.

Aims: To explore if eating disorder symptom prevalence varies according to birth region, parents' birth region and neighbourhood characteristics, and analyse if the observed patterns match the likelihood of being in specialist treatment.

Multiple myeloma risk in relation to long-term air pollution exposure - A pooled analysis of four European cohorts.

Background: Air pollution is a growing concern worldwide, with significant impacts on human health. Multiple myeloma is a type of blood cancer with increasing incidence. Studies have linked air pollution exposure to various types of cancer, including leukemia and lymphoma, however, the relationship with multiple myeloma incidence has not been extensively investigated.

Peripheral blood cellular dynamics of rheumatoid arthritis treatment informs about efficacy of response to disease modifying drugs.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by systemic inflammation and is mediated by multiple immune cell types. In this work, we aimed to determine the relevance of changes in cell proportions in peripheral blood mononuclear cells (PBMCs) during the development of disease and following treatment. Samples from healthy blood donors, newly diagnosed RA patients, and established RA patients that had an inadequate response to MTX and were about to start tumor necrosis factor inhibitors (TNFi) treatment were collected before and after 3 months of treatment.

Molecular signature of methotrexate response among rheumatoid arthritis patients.

Background: Methotrexate (MTX) is the first line treatment for rheumatoid arthritis (RA), but failure of satisfying treatment response occurs in a significant proportion of patients. Here we present a longitudinal multi-omics study aimed at detecting molecular and cellular processes in peripheral blood associated with a successful methotrexate treatment of rheumatoid arthritis.

Methods: Eighty newly diagnosed patients with RA underwent clinical assessment and donated blood before initiation of MTX, and 3 months into treatment.

Characterization of data-driven clusters in diabetes-free adults and their utility for risk stratification of type 2 diabetes.

Background: The prevention of type 2 diabetes is challenging due to the variable effects of risk factors at an individual level. Data-driven methods could be useful to detect more homogeneous groups based on risk factor variability. The aim of this study was to derive characteristic phenotypes using cluster analysis of common risk factors and to assess their utility to stratify the risk of type 2 diabetes.

Breast Cancer Incidence in Relation to Long-Term Low-Level Exposure to Air Pollution in the ELAPSE Pooled Cohort.

Background: Established risk factors for breast cancer include genetic disposition, reproductive factors, hormone therapy, and lifestyle-related factors such as alcohol consumption, physical inactivity, smoking, and obesity. More recently a role of environmental exposures, including air pollution, has also been suggested. The aim of this study, was to investigate the relationship between long-term air pollution exposure and breast cancer incidence.

Exposure to surrounding greenness and natural-cause and cause-specific mortality in the ELAPSE pooled cohort.

Background: The majority of studies have shown higher greenness exposure associated with reduced mortality risks, but few controlled for spatially correlated air pollution and traffic noise exposures. We aim to address this research gap in the ELAPSE pooled cohort.

Methods: Mean Normalized Difference Vegetation Index (NDVI) in a 300-m grid cell and 1-km radius were assigned to participants' baseline home addresses as a measure of surrounding greenness exposure.

Antibodies to a Citrullinated Epitope Are Increased in Early Rheumatoid Arthritis, and Can Be Produced by Gingival Tissue B Cells: Implications for a Bacterial Origin in RA Etiology.

Based on the epidemiological link between periodontitis and rheumatoid arthritis (RA), and the unique feature of the periodontal bacterium to citrullinate proteins, it has been suggested that production of anti-citrullinated protein antibodies (ACPA), which are present in a majority of RA patients, may be triggered in the gum mucosa. To address this hypothesis, we investigated the antibody response to a citrullinated peptide in relation to the autoimmune ACPA response in early RA, and examined citrulline-reactivity in monoclonal antibodies derived from human gingival B cells. Antibodies to a citrullinated peptide derived from (denoted CPP3) and human citrullinated peptides were analyzed by multiplex array in 2,807 RA patients and 372 controls; associations with RA risk factors and clinical features were examined.

Early prediction of clinical response to anti-TNF treatment using multi-omics and machine learning in rheumatoid arthritis.

Objectives: Advances in immunotherapy by blocking TNF have remarkably improved treatment outcomes for Rheumatoid arthritis (RA) patients. Although treatment specifically targets TNF, the downstream mechanisms of immune suppression are not completely understood. The aim of this study was to detect biomarkers and expression signatures of treatment response to TNF inhibition.

Understanding interactions between risk factors, and assessing the utility of the additive and multiplicative models through simulations.

Understanding the genetic background of complex diseases requires the expansion of studies beyond univariate associations. Therefore, it is important to use interaction assessments of risk factors in order to discover whether, and how genetic risk variants act together on disease development. The principle of interaction analysis is to explore the magnitude of the combined effect of risk factors on disease causation.

Presence of autoantibodies in "seronegative" rheumatoid arthritis associates with classical risk factors and high disease activity.

Background: Rheumatoid arthritis (RA) is classified as seropositive or seronegative, depending on the presence/absence of rheumatoid factor (RF), primarily IgM RF, and/or anti-citrullinated protein antibodies (ACPA), commonly detected using anti-cyclic citrullinated peptide (CCP) assays. Known risk factors associate with the more severe seropositive form of RA; less is known about seronegative RA. Here, we examine risk factors and clinical phenotypes in relation to presence of autoantibodies in the RA subset that is traditionally defined as seronegative.

Distinct HLA Associations with Rheumatoid Arthritis Subsets Defined by Serological Subphenotype.

Rheumatoid arthritis (RA) is the most common immune-mediated arthritis. Anti-citrullinated peptide antibodies (ACPA) are highly specific to RA and assayed with the commercial CCP2 assay. Genetic drivers of RA within the MHC are different for CCP2-positive and -negative subsets of RA, particularly at HLA-DRB1.

Tobacco smoking induces changes in true DNA methylation, hydroxymethylation and gene expression in bronchoalveolar lavage cells.

Background: While smoking is known to associate with development of multiple diseases, the underlying mechanisms are still poorly understood. Tobacco smoking can modify the chemical integrity of DNA leading to changes in transcriptional activity, partly through an altered epigenetic state. We aimed to investigate the impact of smoking on lung cells collected from bronchoalveolar lavage (BAL).

Systematic approach demonstrates enrichment of multiple interactions between non- risk variants and risk alleles in rheumatoid arthritis.

Objective: In anti-citrullinated protein antibody positive rheumatoid arthritis (ACPA-positive RA), a particular subset of alleles, called shared epitope (SE) alleles, is a highly influential genetic risk factor. Here, we investigated whether non- single nucleotide polymorphisms (SNP), conferring low disease risk on their own, interact with SE alleles more frequently than expected by chance and if such genetic interactions influence the SE effect concerning risk to ACPA-positive RA.

Methods: We computed the attributable proportion (AP) due to additive interaction at genome-wide level for two independent ACPA-positive RA cohorts: the Swedish epidemiological investigation of rheumatoid arthritis (EIRA) and the North American rheumatoid arthritis consortium (NARAC).

Large-Scale trans-eQTLs Affect Hundreds of Transcripts and Mediate Patterns of Transcriptional Co-regulation.

Efforts to decipher the causal relationships between differences in gene regulation and corresponding differences in phenotype have been stymied by several basic technical challenges. Although detecting local, cis-eQTLs is now routine, trans-eQTLs, which are distant from the genes of origin, are far more difficult to find because millions of SNPs must currently be compared to thousands of transcripts. Here, we demonstrate an alternative approach: we looked for SNPs associated with the expression of many genes simultaneously and found that hundreds of trans-eQTLs each affect hundreds of transcripts in lymphoblastoid cell lines across three African populations.