Early-life and adult body mass index in relation to MS disability progression.

Background And Objectives: The influence of body weight across the life course on multiple sclerosis (MS) progression remains incompletely understood. While excess body mass at diagnosis is associated with disability progression, it is unclear how early-life and adult BMI jointly affect long-term outcomes. We aimed to investigate the separate and combined effects of BMI at age 20 and at diagnosis on MS progression.

Depression Polygenicity and Disease Activity and Disability Worsening in Multiple Sclerosis.

Objective: A better understanding of factors associated with multiple sclerosis (MS) disease activity and disability is needed. Given the strong link between comorbid depression and MS disease activity and disability, we aimed to determine whether the depression genetic burden, as modelled using its polygenic score, is associated with MS disease activity and disability worsening.

Methods: In this cohort study, we used samples from neurologist-defined adult people with MS (PwMS) followed in clinical care or during a clinical trial from existing cohorts: Canada, the United States (US), and Sweden with extensive longitudinal phenotypes.

Immune, Developmental, and Synaptic Pathways Define Bipolar Disorder Clinical Heterogeneity.

Importance: The clinical heterogeneity of bipolar disorder (BD) is a major obstacle to improving diagnosis, predicting patient outcomes, and developing personalized treatments. A genetic approach is needed to deconstruct the disorder and uncover its fundamental biology. Previous genetic studies focusing on broad diagnostic categories have been limited in their ability to parse this complexity.

Education, Lifestyle Risk Factors, and Treatment Choices and Multiple Sclerosis Progression.

Importance: The implications of socioeconomic factors, including educational level, for multiple sclerosis (MS) progression remain unclear. Understanding whether educational level directly affects MS outcomes or is confounded by lifestyle risk factors and treatment choices could inform personalized care strategies.

Objective: To investigate the association between educational level and outcomes related to MS, including worsening of disability, cognition, and health-related quality of life, after adjusting for potential confounding factors or mediation by lifestyle factors and treatment.

Multiomics integration prioritizes potential drug targets for multiple sclerosis.

Multiple sclerosis (MS) is an immune-mediated disease with no current cure. Drug discovery and repurposing are essential to enhance treatment efficacy and safety. We utilized summary statistics for protein quantitative trait loci (pQTL) of 2,004 plasma and 1,443 brain proteins, a genome-wide association study of MS susceptibility with 14,802 cases and 26,703 controls, both bulk and cell-type specific transcriptome data, and external pQTL data in blood and brain.

Nicotine, Alcohol Consumption, and Risk of Myasthenia Gravis: Results From the Swedish Nationwide GEMG Study.

Background And Objectives: Myasthenia gravis (MG), an autoimmune disease characterized by fluctuating muscle weakness, is believed to result from complex gene-environment interactions, yet few risk factors have been identified. The objective of this study was to determine the effect of nicotine and alcohol on MG disease risk.

Methods: The Genes and Environment in Myasthenia Gravis study is a Swedish, nationwide cross-sectional case-control study where prevalent patients with MG were invited to submit an extensive questionnaire on lifestyle and environment.

Brain age in multiple sclerosis: a study with deep learning and traditional machine learning.

'Brain age' is a numerical estimate of the biological age of the brain and an overall effort to measure neurodegeneration, regardless of disease type. In multiple sclerosis, accelerated brain ageing has been linked to disability accrual. Artificial intelligence has emerged as a promising tool for the assessment and quantification of the impact of neurodegenerative diseases.

Bile acid metabolism in multiple sclerosis is perturbed and associated with the risk of confirmed disability worsening.

Background: Bile acids (BAs) have emerged as important mediators in neuroinflammation and neurodegeneration, important features of multiple sclerosis (MS). This study aimed to examine serum BA levels in newly diagnosed people with MS (pwMS) and explore their association with disability worsening.

Methods: The study included 907 pwMS and 907 matched controls from the Swedish population-based EIMS cohort, with clinical follow-up data from the Swedish MS Registry.

Antibody reactivity against EBNA1 and GlialCAM differentiates multiple sclerosis patients from healthy controls.

Multiple sclerosis (MS) is an autoimmune demyelinating disorder of the central nervous system (CNS), which is linked to Epstein-Barr virus (EBV) infection, preceding the disease. The molecular mechanisms underlying this connection are only partially understood. We previously described molecular mimicry between the EBV transcription factor EBV nuclear antigen 1 (EBNA1) and three human CNS proteins: anoctamin-2 (ANO2), alpha-B crystallin (CRYAB), and glial cellular adhesion molecule (GlialCAM).

Impact of lifestyle factors post-infectious mononucleosis on multiple sclerosis risk.

Background: Accumulating evidence suggest that Epstein-Barr virus (EBV) is crucial in the development of multiple sclerosis (MS), with inadequate infection control possibly contributing to disease onset. Past infectious mononucleosis (IM) has been found to interact with smoking, obesity, and sun exposure. We aimed to investigate potential interactions between a history of IM and the following risk factors for MS: passive smoking, alcohol consumption, fish consumption, vitamin D status, adolescent sleep duration and sleep quality.

Associations of PFAS and OH-PCBs with risk of multiple sclerosis onset and disability worsening.

Exposure to per- and polyfluorinated substances (PFAS) and hydroxylated polychlorinated biphenyls (OH-PCBs) is associated with adverse human health effects, including immunosuppression. It is unknown if these substances can affect the course of autoimmune diseases. This study was based on 907 individuals with multiple sclerosis (MS) and 907 matched controls, where the MS cases were followed longitudinally using the Swedish MS register.

Impact of fish consumption on disability progression in multiple sclerosis.

Background: Emerging evidence indicates that diet, including fish consumption, may play a role in the development and progression of multiple sclerosis (MS). We aimed to investigate the influence of fish consumption on disability progression in MS.

Methods: Incident cases from the population-based case-control study Epidemiological Investigation of MS (n=2719), with data on fish intake and Expanded Disability Status Scale (EDSS) outcomes, were categorised by fish consumption and followed up to 15 years post-diagnosis through the Swedish MS registry.

Lifestyle factors associated with benign multiple sclerosis.

Background: Benign multiple sclerosis (MS), characterised by minimal disability despite long disease duration, remains poorly understood in terms of its determinants and prognostic implications. While lifestyle factors have been implicated in modifying disease progression, their role in distinguishing benign and non-benign MS remains unclear.

Methods: We conducted a comparative analysis of patients with benign (n=2040) and non-benign MS (n=4283) using data from Swedish nationwide case-control studies with long-term follow-up.

Smoking and Obesity Interact to Adversely Affect Disease Progression and Cognitive Performance in Multiple Sclerosis.

Background: Smoking and obesity interact to exacerbate the risk of hypertension, diabetes, and cardiovascular disease, but their potential synergistic effects on outcomes in multiple sclerosis (MS) have not been well studied. We aimed to study whether smoking and obesity interact to affect disease progression and cognitive function in patients with MS.

Methods: Incident cases from the population-based case-control study Epidemiological Investigation of MS (EIMS) were categorized by smoking and obesity status at diagnosis and followed up to 15 years postdiagnosis through the Swedish MS registry (n = 3336).

Genomics yields biological and phenotypic insights into bipolar disorder.

Bipolar disorder is a leading contributor to the global burden of disease. Despite high heritability (60-80%), the majority of the underlying genetic determinants remain unknown. We analysed data from participants of European, East Asian, African American and Latino ancestries (n = 158,036 cases with bipolar disorder, 2.

Corroborating written history with ancient DNA: The case of the Well-man described in an Old Norse .

The potential of ancient DNA analyses to provide independent sources of information about events in the historical record remains to be demonstrated. Here we apply palaeogenomic analysis to human remains excavated from a medieval well at the ruins of Sverresborg Castle in central Norway. In , the Old Norse of King Sverre Sigurdsson, one passage details a 1197-CE raid on the castle and mentions a dead man thrown into the well.

Obesity Affects Disease Activity and Progression, Cognitive Functioning, and Quality of Life in People With Multiple Sclerosis.

Background And Objectives: While obesity is a known risk factor of the development of multiple sclerosis (MS), its impact on MS disease progression remains unclear. We aimed to investigate the influence of body mass index (BMI) on disease activity and progression, cognitive performance, and health-related quality of life in patients with MS.

Methods: Patients from an incident population-based case-control study (n = 3,249) were categorized based on BMI status at diagnosis and followed up after diagnosis through the Swedish MS registry.

Exploring the relationship between polycystic ovarian syndrome, testosterone, and multiple sclerosis in women: A nationwide cohort study and genome-wide cross-trait analysis.

Background: Women have a higher risk of developing multiple sclerosis (MS), potentially due to hormonal factors. Elevated testosterone levels, common in polycystic ovary syndrome (PCOS), might influence MS risk.

Objective: To investigate the relationship between PCOS, as a proxy for elevated testosterone levels, and MS risk through phenotypic and genomic analysis.

Pharmacogenomics of clinical response to Natalizumab in multiple sclerosis: a genome-wide multi-centric association study.

Background: Inter-individual differences in treatment response are marked in multiple sclerosis (MS). This is true for Natalizumab (NTZ), to which a subset of patients displays sub-optimal treatment response. We conducted a multi-centric genome-wide association study (GWAS), with additional pathway and network analysis to identify genetic predictors of response to NTZ.

Enhanced and cross-reactive memory B cell response against Epstein-Barr virus nuclear antigen 1 in multiple sclerosis.

Multiple sclerosis (MS) is a prototypical autoimmune disease of the central nervous system (CNS). In addition to CD4 T cells, memory B cells are now recognized as a critical cell type in the disease. This is underlined by the fact that the best-characterized environmental risk factor for MS is the Epstein-Barr virus (EBV), which can infect and persist in memory B cells throughout life.

A genetic-epigenetic interplay at 1q21.1 locus underlies CHD1L-mediated vulnerability to primary progressive multiple sclerosis.

Multiple Sclerosis (MS) is a heterogeneous inflammatory and neurodegenerative disease with an unpredictable course towards progressive disability. Treating progressive MS is challenging due to limited insights into the underlying mechanisms. We examined the molecular changes associated with primary progressive MS (PPMS) using a cross-tissue (blood and post-mortem brain) and multilayered data (genetic, epigenetic, transcriptomic) from independent cohorts.

Adolescent sleep patterns, genetic predisposition, and risk of multiple sclerosis.

Study Objectives: Shift work, insufficient sleep, and poor sleep quality at young age have been associated with increased risk of multiple sclerosis (MS). This study aimed to investigate the potential interaction between aspects of inadequate sleep (short sleep, phase shift, and poor sleep quality) during adolescence and HLA-DRB1*15:01 in relation to MS risk.

Methods: We used a Swedish population-based case-control study (1253 cases and 1766 controls).