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Research paper thumbnail of Lifestyle behaviors in Swedish university students before and during the first six months of the COVID-19 pandemic: a cohort study

BMC Public Health

Background Changes in Swedish university students’ lifestyle behaviors during the COVID-19 pandem... more Background Changes in Swedish university students’ lifestyle behaviors during the COVID-19 pandemic are unknown. This study aimed to assess physical activity, sitting time, meal frequency and risk substance use (alcohol, tobacco, and illicit use of drugs) in Swedish university students before and during the first six months of the COVID-19 pandemic, for all and stratified by age and sex. Methods Data were obtained from the Sustainable University Life cohort study in which web-based surveys were sent to university students repeatedly for one year. Baseline assessment (before the pandemic) was between August 2019-March 2020, follow-up 1 (FU1) between March-June 2020, and follow-up 2 (FU2) between June–September 2020. Participants reported weekly minutes of physical activity, daily sitting hours, meal frequency by weekly intake of different meals, and motivation for eating irregularly, if so. Also, harmful use of alcohol, tobacco and illicit drugs was assessed. Population means and dif...

Research paper thumbnail of The interaction of smoking and the HLA-DRB1 shared epitope in rheumatoid factor-positive rheumatoid arthritis: comment on the article by Padyukov et al - Reply

Research paper thumbnail of OP0052 A Dense Mapping of HLA Region for Study of Interaction with Smoking in the Development of Rheumatoid Arthritis

Annals of the Rheumatic Diseases, 2013

Background: In a recent fine-mapping study using the Immunochip genotyping array, the RUNX1 regio... more Background: In a recent fine-mapping study using the Immunochip genotyping array, the RUNX1 region was associated with rheumatoid arthritis (RA p=5x10-10), juvenile idiopathic arthritis (JIA p=1x10-8) and psoriatic arthritis (PsA p=6x10-4). In each disease the SNP rs9979383 confers disease protection with odds ratios ranging from 0.8-0.9. This SNP maps approximately 290kb upstream of the 3' end of RUNX1, indicating that it may potentially be involved in gene regulation. RUNX1 encodes a master transcription factor which has been shown to interact with the regulatory T cell transcription factor FOXP3 as well as regulation of skeletal development. Unlike many loci on the Immunochip array, variation in the RUNX1 region is not well covered, therefore further fine mapping is required. Objectives: To fine map the RUNX1 region and select a SNP suitable for expression studies. Methods: As rs9979383 lies between two points of high recombination, SNPs between these points were selected for fine mapping. 42 common (MAF>0.05) tag SNPs (r 2 >0.9) from the Utah residents (CEPH) with Northern and Western European ancestry (CEU) 1000 genomes July 2010 release were selected using Haploview v.4.2. 2255 RA cases and 1877 healthy controls from the United Kingdom Rheumatoid Arthritis Genetics Group (UKRAGG) were genotyped using the Sequenom iPlex MassARRAY platform. SNPs and samples which reached >90% success rate were included in the analysis. Allelic association testing was performed using PLINK v.1.07 and functional annotation of SNPs was performed using the ASSIMILATOR software programme. Results: In the UKRAG cohort, association with rs9979383 was replicated (p=0.02, OR = 0.9, CI 95% 0.82-0.98) with an odds ratio of 0.9, identical to the previous RA study. No other SNPs in the region showed evidence for association. RUNX1 is highly expressed in CD33+ progenitor cells which are important in generation of immune cells and vascularisation of the synovium. Functional annotation of this SNP indicates that it lies within a region of open chromatin with transcription factor binding potential, making it an ideal candidate for gene expression studies. Conclusions: These results indicate that the RUNX1 association is localised to r99793983 in this RA cohort. This will require further investigation in independent JIA and PsA cohorts but provides evidence that the region is associated with different types of inflammatory arthritis. Currently both whole blood and cell specific expression of the RUNX1 region are underway using individuals with differential genotypes at rs9979383. Combined with the fine mapping this will inform further investigations of the role of RUNX1 in the common pathogenesis of inflammatory arthritis.

Research paper thumbnail of Parity and the risk of developing rheumatoid arthritis: results from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study

Annals of the rheumatic diseases, 2014

To study the impact of parity history on the risk of antibodies to citrullinated peptide antigens... more To study the impact of parity history on the risk of antibodies to citrullinated peptide antigens (ACPA) positive and ACPA-negative rheumatoid arthritis (RA), in different age-groups. Data from a population-based case-control study of female incident RA cases were analysed (2035 cases and 2911 controls, aged 18-70 years ). Parity history was assessed through a questionnaire. Parous women were compared with nulliparous, by calculating odds ratios (ORs) with 95% confidence interval (CI). Parity was associated with an increased risk of ACPA-negative RA in women aged 18-44 years (OR=2.1, 95% CI 1.4 to 3.2), but not in those aged 45-70 years (OR=0.9, 95% CI 0.7 to 1.3). Among young women, an increased risk of ACPA-negative RA was found in those who gave birth during the year of symptom onset (OR=2.6, 95% CI 1.4 to 4.8) and who were at a young age at first birth (<23) (OR=2.5, 95% CI 1.5 to 4.1). Parity and the postpartum period were not associated with ACPA-positive RA, but older age ...

Research paper thumbnail of A gene-gene interaction between PTPN22 and HLA-DRB1 SE genes regarding anti-CCP positive RA. Results from the Swedish eira study

Research paper thumbnail of Is there a gene-environment interaction between smoking and PTPN22 regarding anti-CCP positive RA? Results from the Swedish EIRA study

Research paper thumbnail of A gene-gene interaction between PTPN22 and HLA-DRB1 SE alleles regarding anti-CCP positive rheumatoid arthritis. Results from the Swedish EIRA study

Research paper thumbnail of Gene-environment interaction involving HLA-DRB1 shared epitope Alleles and smoking in ACPA-positive rheumatoid arthritis

Research paper thumbnail of CITRULLINATED alpha-ENOLASE: A MAJOR AUTOANTIGEN LINKING SMOKING AND HLA-DRB1 SHARED EPITOPE TO RHEUMATOID ARTHRITIS

Research paper thumbnail of Ethanol consumption is associated with decreased risks for developing RA results from the Swedish EIRA study

Research paper thumbnail of Familial risks and heritability of RA in relation to RF/ACPA status, number and type of affected relatives, sex and age

ABSTRACT To estimate the familial aggregation of RA in three large population-representative samp... more ABSTRACT To estimate the familial aggregation of RA in three large population-representative samples, and to test if the familial aggregation is modified by type of relative, sex, RF/ACPA-status, and age at RA onset. A Register-based nested case-control study was performed in the Swedish total population. RA was ascertained through the nationwide Patient register (N=88,639), the clinical Swedish Rheumatology Quality register (N=11,519), and the EIRA case-control study (N=2,871). First and second degree relatives were ascertained through the Swedish Multi-Generation Register. Familial risks where calculated using conditional logistic regression. Consistent across data sources, the familial OR for RA was about 3 in first degree relatives of RA patients, and 2 in second degree relatives. The familial risks were similar among siblings, parents and offspring. The familial aggregation was not modified by sex, but was higher for RA with early onset, and for RF/ACPA-positive RA. The observed familial risks were consistent with a heritability for ACPA-positive RA of around 50% and for ACPA-negative RA of about 20%. The pattern of risks suggests that familial factors influence RA in men and women equally, and that these factors are of less importance for late onset RA. Familial factors are more important for seropositive RA, but there is a significant familial overlap between seropositive and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest a heritability of RA lower than previously reported, in particular for ACPA-negative RA.

Research paper thumbnail of Smoking is associated with anti-CCP positive RA in a dose dependent manner, results from the swedish EIRA study

Research paper thumbnail of A new model for an etiology of RA; Smoking may trigger HLA-DR (SE)-restricted immune reactions to autoantigens modified by citruillination

Research paper thumbnail of John Bowes, 5, 6 Leonid Padyukov, 7 Yukinori Okada, Miguel A. González-Gay, 10 Solbritt Rantapää-Dahlqvist, 11 Javier Martin, 12 Tom WJ Huizinga, 8 Robert M. Plenge, 13 Jane Worthington, 5, 6 Peter K. Gregersen, 14 Lars Klareskog, 7 Paul IW de Bakker

John Bowes, 5, 6 Leonid Padyukov, 7 Yukinori Okada, Miguel A. González-Gay, 10 Solbritt Rantapää-Dahlqvist, 11 Javier Martin, 12 Tom WJ Huizinga, 8 Robert M. Plenge, 13 Jane Worthington, 5, 6 Peter K. Gregersen, 14 Lars Klareskog, 7 Paul IW de Bakker

Research paper thumbnail of Familial Risks of Ra in Relation to Type of Affected Relatives, Age, Sex, and RF/Acpa

Research paper thumbnail of To Which Extent May the Familial Risk of RA be Explained by Established RA Risk Factors?

Research paper thumbnail of Regional differences regarding risk of developing rheumatoid arthritis in Stockholm County, Sweden: results from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study

Scandinavian Journal of Rheumatology, 2013

Objectives-Rheumatoid arthritis (RA) is a complex disease that is associated with genetic and env... more Objectives-Rheumatoid arthritis (RA) is a complex disease that is associated with genetic and environmental factors. We have investigated geospatial variation in risk of developing RA within Stockholm County, with respect to established environmental risk factors for RA, as well as serologically-defined subgroups of RA. Methods-Information regarding geographical location for 1432 cases and 2529 controls from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, living in Stockholm County at RA symptom onset, or matched date for controls, was used to estimate geospatial variation in risk. We used Generalized Additive Models (GAM) to create a risk surface, calculate odds ratios and adjust for potential confounding by smoking, educational level and RA within

Research paper thumbnail of Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis

Research paper thumbnail of Silica exposure is associated with increased risk of developing rheumatoid arthritis: results from the Swedish EIRA study

Annals of the Rheumatic Diseases, 2005

Research paper thumbnail of Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile

Annals of the Rheumatic Diseases, 2012

Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis define... more Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile.

Research paper thumbnail of Lifestyle behaviors in Swedish university students before and during the first six months of the COVID-19 pandemic: a cohort study

BMC Public Health

Background Changes in Swedish university students’ lifestyle behaviors during the COVID-19 pandem... more Background Changes in Swedish university students’ lifestyle behaviors during the COVID-19 pandemic are unknown. This study aimed to assess physical activity, sitting time, meal frequency and risk substance use (alcohol, tobacco, and illicit use of drugs) in Swedish university students before and during the first six months of the COVID-19 pandemic, for all and stratified by age and sex. Methods Data were obtained from the Sustainable University Life cohort study in which web-based surveys were sent to university students repeatedly for one year. Baseline assessment (before the pandemic) was between August 2019-March 2020, follow-up 1 (FU1) between March-June 2020, and follow-up 2 (FU2) between June–September 2020. Participants reported weekly minutes of physical activity, daily sitting hours, meal frequency by weekly intake of different meals, and motivation for eating irregularly, if so. Also, harmful use of alcohol, tobacco and illicit drugs was assessed. Population means and dif...

Research paper thumbnail of The interaction of smoking and the HLA-DRB1 shared epitope in rheumatoid factor-positive rheumatoid arthritis: comment on the article by Padyukov et al - Reply

Research paper thumbnail of OP0052 A Dense Mapping of HLA Region for Study of Interaction with Smoking in the Development of Rheumatoid Arthritis

Annals of the Rheumatic Diseases, 2013

Background: In a recent fine-mapping study using the Immunochip genotyping array, the RUNX1 regio... more Background: In a recent fine-mapping study using the Immunochip genotyping array, the RUNX1 region was associated with rheumatoid arthritis (RA p=5x10-10), juvenile idiopathic arthritis (JIA p=1x10-8) and psoriatic arthritis (PsA p=6x10-4). In each disease the SNP rs9979383 confers disease protection with odds ratios ranging from 0.8-0.9. This SNP maps approximately 290kb upstream of the 3' end of RUNX1, indicating that it may potentially be involved in gene regulation. RUNX1 encodes a master transcription factor which has been shown to interact with the regulatory T cell transcription factor FOXP3 as well as regulation of skeletal development. Unlike many loci on the Immunochip array, variation in the RUNX1 region is not well covered, therefore further fine mapping is required. Objectives: To fine map the RUNX1 region and select a SNP suitable for expression studies. Methods: As rs9979383 lies between two points of high recombination, SNPs between these points were selected for fine mapping. 42 common (MAF>0.05) tag SNPs (r 2 >0.9) from the Utah residents (CEPH) with Northern and Western European ancestry (CEU) 1000 genomes July 2010 release were selected using Haploview v.4.2. 2255 RA cases and 1877 healthy controls from the United Kingdom Rheumatoid Arthritis Genetics Group (UKRAGG) were genotyped using the Sequenom iPlex MassARRAY platform. SNPs and samples which reached >90% success rate were included in the analysis. Allelic association testing was performed using PLINK v.1.07 and functional annotation of SNPs was performed using the ASSIMILATOR software programme. Results: In the UKRAG cohort, association with rs9979383 was replicated (p=0.02, OR = 0.9, CI 95% 0.82-0.98) with an odds ratio of 0.9, identical to the previous RA study. No other SNPs in the region showed evidence for association. RUNX1 is highly expressed in CD33+ progenitor cells which are important in generation of immune cells and vascularisation of the synovium. Functional annotation of this SNP indicates that it lies within a region of open chromatin with transcription factor binding potential, making it an ideal candidate for gene expression studies. Conclusions: These results indicate that the RUNX1 association is localised to r99793983 in this RA cohort. This will require further investigation in independent JIA and PsA cohorts but provides evidence that the region is associated with different types of inflammatory arthritis. Currently both whole blood and cell specific expression of the RUNX1 region are underway using individuals with differential genotypes at rs9979383. Combined with the fine mapping this will inform further investigations of the role of RUNX1 in the common pathogenesis of inflammatory arthritis.

Research paper thumbnail of Parity and the risk of developing rheumatoid arthritis: results from the Swedish Epidemiological Investigation of Rheumatoid Arthritis study

Annals of the rheumatic diseases, 2014

To study the impact of parity history on the risk of antibodies to citrullinated peptide antigens... more To study the impact of parity history on the risk of antibodies to citrullinated peptide antigens (ACPA) positive and ACPA-negative rheumatoid arthritis (RA), in different age-groups. Data from a population-based case-control study of female incident RA cases were analysed (2035 cases and 2911 controls, aged 18-70 years ). Parity history was assessed through a questionnaire. Parous women were compared with nulliparous, by calculating odds ratios (ORs) with 95% confidence interval (CI). Parity was associated with an increased risk of ACPA-negative RA in women aged 18-44 years (OR=2.1, 95% CI 1.4 to 3.2), but not in those aged 45-70 years (OR=0.9, 95% CI 0.7 to 1.3). Among young women, an increased risk of ACPA-negative RA was found in those who gave birth during the year of symptom onset (OR=2.6, 95% CI 1.4 to 4.8) and who were at a young age at first birth (<23) (OR=2.5, 95% CI 1.5 to 4.1). Parity and the postpartum period were not associated with ACPA-positive RA, but older age ...

Research paper thumbnail of A gene-gene interaction between PTPN22 and HLA-DRB1 SE genes regarding anti-CCP positive RA. Results from the Swedish eira study

Research paper thumbnail of Is there a gene-environment interaction between smoking and PTPN22 regarding anti-CCP positive RA? Results from the Swedish EIRA study

Research paper thumbnail of A gene-gene interaction between PTPN22 and HLA-DRB1 SE alleles regarding anti-CCP positive rheumatoid arthritis. Results from the Swedish EIRA study

Research paper thumbnail of Gene-environment interaction involving HLA-DRB1 shared epitope Alleles and smoking in ACPA-positive rheumatoid arthritis

Research paper thumbnail of CITRULLINATED alpha-ENOLASE: A MAJOR AUTOANTIGEN LINKING SMOKING AND HLA-DRB1 SHARED EPITOPE TO RHEUMATOID ARTHRITIS

Research paper thumbnail of Ethanol consumption is associated with decreased risks for developing RA results from the Swedish EIRA study

Research paper thumbnail of Familial risks and heritability of RA in relation to RF/ACPA status, number and type of affected relatives, sex and age

ABSTRACT To estimate the familial aggregation of RA in three large population-representative samp... more ABSTRACT To estimate the familial aggregation of RA in three large population-representative samples, and to test if the familial aggregation is modified by type of relative, sex, RF/ACPA-status, and age at RA onset. A Register-based nested case-control study was performed in the Swedish total population. RA was ascertained through the nationwide Patient register (N=88,639), the clinical Swedish Rheumatology Quality register (N=11,519), and the EIRA case-control study (N=2,871). First and second degree relatives were ascertained through the Swedish Multi-Generation Register. Familial risks where calculated using conditional logistic regression. Consistent across data sources, the familial OR for RA was about 3 in first degree relatives of RA patients, and 2 in second degree relatives. The familial risks were similar among siblings, parents and offspring. The familial aggregation was not modified by sex, but was higher for RA with early onset, and for RF/ACPA-positive RA. The observed familial risks were consistent with a heritability for ACPA-positive RA of around 50% and for ACPA-negative RA of about 20%. The pattern of risks suggests that familial factors influence RA in men and women equally, and that these factors are of less importance for late onset RA. Familial factors are more important for seropositive RA, but there is a significant familial overlap between seropositive and seronegative RA. Even if the familial risk is assumed to be completely due to genetics, the observed risks suggest a heritability of RA lower than previously reported, in particular for ACPA-negative RA.

Research paper thumbnail of Smoking is associated with anti-CCP positive RA in a dose dependent manner, results from the swedish EIRA study

Research paper thumbnail of A new model for an etiology of RA; Smoking may trigger HLA-DR (SE)-restricted immune reactions to autoantigens modified by citruillination

Research paper thumbnail of John Bowes, 5, 6 Leonid Padyukov, 7 Yukinori Okada, Miguel A. González-Gay, 10 Solbritt Rantapää-Dahlqvist, 11 Javier Martin, 12 Tom WJ Huizinga, 8 Robert M. Plenge, 13 Jane Worthington, 5, 6 Peter K. Gregersen, 14 Lars Klareskog, 7 Paul IW de Bakker

John Bowes, 5, 6 Leonid Padyukov, 7 Yukinori Okada, Miguel A. González-Gay, 10 Solbritt Rantapää-Dahlqvist, 11 Javier Martin, 12 Tom WJ Huizinga, 8 Robert M. Plenge, 13 Jane Worthington, 5, 6 Peter K. Gregersen, 14 Lars Klareskog, 7 Paul IW de Bakker

Research paper thumbnail of Familial Risks of Ra in Relation to Type of Affected Relatives, Age, Sex, and RF/Acpa

Research paper thumbnail of To Which Extent May the Familial Risk of RA be Explained by Established RA Risk Factors?

Research paper thumbnail of Regional differences regarding risk of developing rheumatoid arthritis in Stockholm County, Sweden: results from the Swedish Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study

Scandinavian Journal of Rheumatology, 2013

Objectives-Rheumatoid arthritis (RA) is a complex disease that is associated with genetic and env... more Objectives-Rheumatoid arthritis (RA) is a complex disease that is associated with genetic and environmental factors. We have investigated geospatial variation in risk of developing RA within Stockholm County, with respect to established environmental risk factors for RA, as well as serologically-defined subgroups of RA. Methods-Information regarding geographical location for 1432 cases and 2529 controls from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) study, living in Stockholm County at RA symptom onset, or matched date for controls, was used to estimate geospatial variation in risk. We used Generalized Additive Models (GAM) to create a risk surface, calculate odds ratios and adjust for potential confounding by smoking, educational level and RA within

Research paper thumbnail of Bayesian inference analyses of the polygenic architecture of rheumatoid arthritis

Research paper thumbnail of Silica exposure is associated with increased risk of developing rheumatoid arthritis: results from the Swedish EIRA study

Annals of the Rheumatic Diseases, 2005

Research paper thumbnail of Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile

Annals of the Rheumatic Diseases, 2012

Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis define... more Genetic and environmental determinants for disease risk in subsets of rheumatoid arthritis defined by the anticitrullinated protein/peptide antibody fine specificity profile.