Anna Karin Hedström

Karolinska Institutet | KI · Department of Clinical Neuroscience, Institute of Environmental Medicine

Compelling evidence indicates that Epstein Barr virus (EBV) infection is a prerequisite for multiple sclerosis (MS). The disease may arise from a complex interplay between latent EBV infection, genetic predisposition, and various environmental and lifestyle factors that negatively affect immune control of the infection. Evidence of gene-environment...

Oluf Andersen,1 Ingemar Ernberg,2 Anna Karin Hedström3 1Department of Clinical Neuroscience, Institute of Neuroscience and Physiology, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden; 2Department of Microbiology, Tumor and Cell Biology, Biomedicum Q8C, Karolinska Institutet, Stockholm, 171 77, Sweden; 3Department of Clinical Neuro...

Objective: There is some evidence implicating diet in the development of inflammatory diseases. We aimed to study the influence of dietary habits on the risk of developing multiple sclerosis (MS). Methods: We used a population-based case-control study recruiting incident cases of MS (1953 cases, 3557 controls). Subjects with different dietary ha...

Unlabelled: We aimed to study the influence of smoking habits, exposure to passive smoking and snuff use on disease progression, cognitive performance and quality of life in patients with multiple sclerosis (MS). Method: Patients from two population-based case-control studies were categorised based on tobacco exposure at diagnosis and were follo...

Background: The associaton between socioeconomic status (SES) and the risk of multiple sclerosis (MS) is unclear. We aimed at studying whether a potential association between indicators of SES and MS risk in Sweden is explained by lifestyle/environmental factors. Method: Using the Swedish MS-registry and the Swedish patient registries, we perfor...

Background Shift work, which often results in sleep deprivation and circadian desynchrony, has been associated with increased risk of multiple sclerosis (MS). We aimed at studying the impact of sleep duration, circadian disruption and sleep quality on MS risk. Methods We used a Swedish population-based case-control study (2075 cases, 3164 controls...

Background Smoking and occupational pulmonary irritants contribute to multiple sclerosis (MS) development. We aimed to study the association between ambient air pollution and MS risk and potential interaction with the human leukocyte antigen (HLA)-DRB1*15:01 allele. Methods Exposure to combustion-related air pollution was estimated as outdoor leve...

Objective: Multiple studies have found a relationship between alcohol consumption and disease activity in rheumatoid arthritis (RA) although reverse causation has been suggested to explain the association. We aimed to study the relationship between alcohol consumption and disease activity, disease progression and health-related quality of life in...

Objective: Inconclusive findings have been reported regarding the influence of smoking on outcomes in established rheumatoid arthritis (RA). We aimed to study the influence of smoking habits on disease activity and health-related quality of life in patients with RA. Methods: Patients with newly diagnosed RA (N=1531) from the population-based cas...

Objectives To investigate the association between psychosocial vulnerability, defined as either low social support or low decision latitude at work, and disease remission at 3, 12, and 60 months in patients with rheumatoid arthritis (RA). Methods This cohort study included all patients enrolled in both the Swedish Epidemiological Investigation of...

Previous studies have observed an inverse association between alcohol consumption and multiple sclerosis (MS) risk. We aimed to investigate possible interactions between alcohol consumption, MS-associated human leukocyte antigen (HLA) genes and smoking regarding MS risk. We used a Swedish population-based case–control study (2059 incident cases, 28...

Background The latitude gradient in multiple sclerosis incidence indicates that low sun exposure and therefore vitamin D deficiency is associated with multiple sclerosis risk. Objective Investigation of the effect of month of birth, which influences postnatal vitamin D levels, on multiple sclerosis risk and severity in Sweden. Methods Patients an...

Background Among multiple sclerosis (MS) patients, an association has been observed between low levels of vitamin D and high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels. However, whether sun exposure/vitamin D moderates the role of Epstein-Barr virus infection in MS etiology is unclear. We aimed to investigate potential synergistic effe...

Background: Infection with human herpesvirus 6A (HHV-6A) has been suggested to increase multiple sclerosis (MS) risk. However, potential interactions between HHV-6A and environmental/lifestyle risk factors for MS have not previously been studied. Methods: We used two Swedish population-based case-control studies comprising 5993 cases and 5995 cont...

Background The role of psychosocial conditions on the disease course of rheumatoid arthritis (RA) is getting increased attention. In our previous study, low social support and low decision latitude at work were associated with known modifiable risk factors for RA disease development, such as smoking and low educational level (1). Further, smoking a...

Objective It has been debated whether the different clinical disease courses in multiple sclerosis (MS) are the consequence of different pathogenic mechanisms, with distinct risk factors, or if all MS clinical phenotypes are variations of similar underlying disease mechanisms. We aimed to study environmental risk factors and their interactions with...

Objective We aimed to investigate the influence of environmental risk factors for multiple sclerosis (MS) in different genetic contexts, and study if interactions between environmental factors and human leucocyte antigen (HLA) genes differ in magnitude according to heterozygocity and homozygocity for HLA-DRB1*15:01 . Methods Using population-based...

Objectives Despite an association between obesity and multiple sclerosis (MS), very little is known regarding the safety and efficacy outcomes for patients with MS and severe obesity undergoing metabolic surgery. The aim of the present study was to evaluate early complications and efficacy outcomes of metabolic surgery in patients with severe obesi...

Objective Because obesity affects the cellular immune response to infections, we aimed to investigate whether high body mass index (BMI) in young adulthood and high Epstein-Barr nuclear antigen 1 (EBNA-1) antibody levels interact with regard to MS risk. We also aimed at exploring potential 3-way interactions between BMI at age 20 years, aspects of...

Objective Previous studies investigating the association between nightmares and suicide have yielded different results. We aimed to investigate whether nightmares, directly or indirectly, influence the incidence of suicide. Methods We used a prospective cohort study, based on 40,902 participants with a mean follow-up duration of 19.0 years. Cox pr...

Objective Several, but not all studies, have shown a dose-dependent inverse association with alcohol consumption and rheumatoid arthritis (RA), whereas smoking is an established risk factor for RA. We aimed to study the association between alcohol consumption and RA incidence and investigate a potential interaction between alcohol and smoking habit...

The prevalence of multiple sclerosis (MS) differs between different regions of Iran. This study aimed to investigate changes in prevalence and incidence rates of MS in ten ethnic and cultural zones of Iran set by the Ministry of Health and Medical Education. The prevalence and incidence of MS have been rapidly increasing in all regions of Iran, espec...

Study Objectives The relationship between insomnia and suicide risk is not completely understood. We aimed to investigate the influence of insomnia on suicide risk, taking both sleep duration and depression into consideration. Methods The present study is based on a Swedish prospective cohort study of 38,786 participants with a mean follow-up time...

Studies using cotinine levels to define smokers have generally failed to detect an association between smoking and multiple sclerosis (MS). Using a Swedish population-based case-control study, we show that associations in relation to MS risk and progression differ considerably depending on how smoking is measured. The risk of conversion into second...

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 seropositi...

It is unclear whether smoking interacts with different aspects of Epstein–Barr virus (EBV) infection with regard to multiple sclerosis (MS) risk. We aimed to investigate whether smoking acts synergistically with elevated EBNA-1 antibody levels or infectious mononucleosis (IM) history regarding MS risk. Two Swedish population-based case–control stud...

Background The potential relationship between perceived cognitive impairment (PCI) and sexual dysfunction in Multiple Sclerosis (MS) has not been studied. Objectives To explore the relationship between cognitive impairment and sexual dysfunction over 2.5 years in people with MS. Methods Data were derived from the Health Outcomes and Lifestyle In...

Potential long‐term consequences of hypnotics remain controversial. We used the prospective Swedish National March Cohort, a study based on 41,695 participants with a mean follow‐up duration of 18.9 years. Logistic regression models and Cox proportional hazards models with attained age as timescale were used to assess associations of hypnotic use w...

Objective We aimed to investigate the influence of lean and fatty fish consumption on MS risk and to what extent a potential effect may be mediated by vitamin D. We also studied the interplay between fish consumption, sun exposure, DRB1*15:01 , and A*02:01 . Methods We used 2 population-based case-control studies (6,914 cases and 6,590 controls)....

Objective We aimed to study (1) to what extent the influence of low sun exposure on multiple sclerosis (MS) risk is mediated by low vitamin D levels; (2) whether low sun exposure or vitamin D deficiency act synergistically with HLA-DRB1*15:01 and absence of HLA-A*02:01. Methods We used two population-based case–control studies (7069 cases, 6632 ma...

Objective Previous studies investigating the association between nightmares and suicide have yielded different results. We aimed to investigate whether nightmares, directly or indirectly, influence the incidence of suicide. Methods We used a prospective cohort study, based on 40,902 participants with a mean follow-up duration of 19.0 years. Cox pr...

Background Breastfeeding as an infant appears protective against later development of some autoimmune diseases, but research into its influence on multiple sclerosis (MS) risk has yielded inconclusive results. Objective We investigated the possible impact of breastfeeding on MS risk. Methods We used two population-based case–control studies compr...

Objective: Elevated levels of anti-EBNA-1 antibodies and infectious mononucleosis (IM) history have consistently been associated with multiple sclerosis (MS) risk. We aimed to study whether these aspects of Epstein–Barr virus (EBV) infection represent separate risk factors for MS and whether they both interact with MS-associated HLA genes in diseas...

Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS c...

Background: Previous studies investigating the relationship between insomnia and mortality have been inconsistent. Purpose: We aimed to assess whether nocturnal insomnia symptoms and non-restorative sleep are associated with all-cause mortality and whether they modify the associations between short and long sleep duration and all-cause mortality...

Background HLA-DRB1*15:01, absence of HLA-A*02:01, and smoking interact to increase multiple sclerosis (MS) risk. Objective To analyze whether MS-associated human leukocyte antigen (HLA) alleles, apart from DRB1*15:01 and absence of A*02:01, interact with smoking in MS development, and to explore whether the established HLA-smoking interaction is...

Human herpesvirus (HHV)-6A or HHV-6B involvement in multiple sclerosis (MS) etiology has remained controversial mainly due to the lack of serological methods that can distinguish the two viruses. A novel multiplex serological assay measuring IgG reactivity against the immediate-early protein 1 from HHV-6A (IE1A) and HHV-6B (IE1B) was used in a MS c...

Background: A rising trend for incidence of multiple sclerosis (MS) has been observed during the recent years in Iran. Several factors have been investigated as the reason, but socio-economic determinants have been neglected. The present study aimed to investigate the relationship between Human Development Index (HDI), income and education and MS...

Objectives The relationship between alcohol consumption and risk for rheumatoid arthritis (RA) is incompletely understood. We aimed to determine the influence of alcohol on anticitrullinated protein antibody (ACPA) positive and ACPA-negative RA and investigate potential interactions between alcohol consumption, smoking and the presence of human leu...

Objectives Previous studies on rheumatoid arthritis (RA) and body mass index (BMI) have yielded diverging results. We aimed to clarify the influence of BMI on the risk of developing anticitrullinated peptide antibody (ACPA)-positive and ACPA-negative RA by taking into consideration gender, smoking habits and human leukocyte antigen (HLA-DRB1) share...

Purpose We endeavored to investigate whether previous findings of an association between antemortem exposure to selective serotonin re-uptake inhibitors (SSRI) and method of suicide could be replicated. Methods Using the Swedish National Board of Forensic Medicine’s toxicology database and the Swedish National Board of Health and Welfare’s nationa...

Objectives Smoking is associated with increased risk for subsets of RA defined by the presence of anti‐citrulline protein antibodies (ACPA) and rheumatoid factors (RF) and an interaction between smoking and HLA‐DRB1 SE has been confined to risk of seropositive RA. We aimed to investigate the interplay between smoking and HLA‐DRB1 SE with regard to...

The etiology of multiple sclerosis (MS) involves multifaceted interactions between genetic loci and environmental factors. Smoking is an important risk factor for MS that overall increases the risk of the disease with approximately 50%. However, the precise effects of smoking on MS development vary considerably in different contexts and in differen...

Objective: We hypothesize that different sources of lung irritation may contribute to elicit an immune reaction in the lungs and subsequently lead to multiple sclerosis (MS) in people with a genetic susceptibility to the disease. We aimed to investigate the influence of exposure to organic solvents on MS risk, and a potential interaction between o...

Background: Multiple sclerosis (MS) incidence has increased recently, particularly in women, suggesting a possible role of one or more environmental exposures in MS risk. The study objective was to determine if animal, dietary, recreational, or occupational exposures are associated with MS risk. Methods: Least absolute shrinkage and selection op...

Extensive evidence indicates that alcohol has significant dose-dependent immunomodulatory properties. The aim of this study was to investigate the possible influence of alcohol consumption on the risk of developing MS, and to relate the influence of alcohol to the effects of smoking.

Obesity in childhood and during adolescence has repeatedly been associated with increased risk of developing MS. In the present study, we aimed to investigate whether the most critical period occurs during childhood or later, during adolescence.

Using two case-control studies, we investigated potential interactions between adolescent obesity and MS risk HLA genes, in relation to the risk of developing MS.

The purpose of the study was to estimate the influence of passive smoking on the risk of developing MS.

The recently demonstrated interaction between smoking and HLA complex genes with regard to MS risk shows that the risk conveyed by an environmental factor may substantially differ depending on genetic background. Using the same Swedish population-based case-control study, and an American prevalent case-control study, we aimed to investigate whether...

The aim of this study was to investigate how age at smoking debut, duration, intensity and cumulative dose of smoking, and smoking cessation influence the association between smoking and MS risk.

Using data from 6 independent studies from 5 different countries, we aimed to investigate whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated and extended to include other populations.

We confirm a previous report of an association between obesity in adolescence and increased MS risk among females and extend this observation to include males.

Neutralizing antibodies (NAbs) to interferon β (IFNβ) products that develop during treatment are associated with a loss of clinical efficacy. The aim of this study was to investigate the influence of smoking habits on the risk of developing NAbs to IFNβ in the treatment of multiple sclerosis (MS).

We investigated the possible impact of exposure to organic solvents on MS risk, and a potential interaction between exposure to organic solvents and MS risk HLA genes.

The aim of this study was to investigate the potential association between reproductive history and MS risk.

The aim of this study was to investigate the potential association between permanent night shift work, rotating shift work, and day oriented shift work, and risk of developing the two major subsets of RA.

The aim of this study was to investigate the potential association between shift work and MS risk.

Recent studies indicate that exposure to nicotine could modulate immune responses within the CNS and nicotine has been shown to be protective in several models of inflammatory diseases. Using two population-based, case-control studies, we investigated the impact of snuff use on MS risk.

The aim of this study was to investigate the potential association between permanent night shift work, rotating shift work, and day oriented shift work, and risk of developing the two major subsets of RA.

The aim of this study was to estimate the influence of passive smoking on the risk of developing anti-citrullinated peptide antibody (ACPA) positive and ACPA negative RA.

Smoking is one of the most established risk factors for rheumatoid arthritis (RA). The aim of this study was to estimate how age at smoking debut, smoking cessation, duration, intensity, and cumulative dose of smoking influence the risk of developing anti-citrullinated peptide antibody (ACPA) positive and ACPA negative RA.

Both high body mass index (BMI) and smoking tobacco are known risk factors for developing multiple sclerosis (MS). However, it is unclear whether BMI, like smoking, is a risk factor for the secondary progressive (SP) course. We, therefore, sought to determine if high/low BMI at age 20 is associated to risk of SP development, in the context of smoki...

Introduction Smoking has consistently been associated with increased risk of developing rheumatoid arthritis (RA). The aim of this study was to estimate the influence of passive smoking on the risk of developing anti-cyclic citrullinated peptide antibodies (ACPA)-positive and ACPA-negative RA. Methods A population-based case–control study using in...

Smoking is one of the most established risk factors for rheumatoid arthritis (RA). The aim of this study was to estimate how age at smoking debut, smoking cessation, duration, intensity, and cumulative dose of smoking influence the risk of developing anti-citrullinated peptide antibodies (ACPA) positive and ACPA negative RA. The present report is b...

Introduction Shift work has previously been associated with increased RA risk in females. The aim of this study was to investigate the potential association between permanent night shift work, rotating shift work, and day oriented shift work, and risk of developing anti- citrullinated peptide antibodies (ACPA) positive and ACPA negative RA. Method...

Background: Strong evidence supports the role of both genetic and environmental factors in pediatric-onset multiple sclerosis (POMS) etiology. Objective: We comprehensively investigated the association between established major histocompatibility complex (MHC) and non-MHC adult multiple sclerosis (MS)-associated variants and susceptibility to PO...

Interactions between environment and genetics may contribute to multiple sclerosis (MS) development. We investigated whether the previously observed interaction between smoking and HLA genotype in the Swedish population could be replicated, refined and extended to include other populations. We used six independent case–control studies from five dif...

Background Environmental factors play a prominent role in rheumatoid arthritis (RA) aetiology. Shift work has previously been associated with increased RA risk in females. The aim of this study was to investigate the potential association, including a dose–response association, between permanent night shift work, rotating shift work and day-oriente...

Background Smoking has consistently been associated with increased risk of developing rheumatoid arthritis (RA). However, no studies have been performed investigating the effect of exposure to environmental tobacco smoke (i.e. passive smoking) on RA risk. Objectives The aim of this study was to estimate the influence of passive smoking on the risk...

In this paper we develop a general framework for quantifying how binary risk factors jointly influence a binary outcome. Our key result is an additive expansion of odds ratios as a sum of marginal effects and interaction terms of varying order. These odds ratio expansions are used for estimating the excess odds ratio, attributable proportion and sy...

Objective: To utilize Mendelian randomization to estimate the causal association between low serum vitamin D concentrations, increased body mass index (BMI), and pediatric-onset multiple sclerosis (MS) using genetic risk scores (GRS). Methods: We constructed an instrumental variable for vitamin D (vitD GRS) by computing a GRS for 3 genetic varia...

Multiple sclerosis (MS) is an autoimmune disease with both genetic and environmental risk factors. Recent studies indicate that childhood and adolescent obesity double the risk of MS, but this association may reflect unmeasured confounders rather than causal effects of obesity. We used separate-sample Mendelian randomization to estimate the causal...

Objectives: The aim of this study was to identify factors influencing the long-term clinical progression of multiple sclerosis (MS). A special objective was to investigate whether early treatment decisions influence outcome. Methods: We included 639 patients diagnosed with MS from 2001 to 2007. The median follow-up time was 99 months (8.25 years...