| 1. |
- Eriksson, Daniel, et al.
(författare)
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Common genetic variation in the autoimmune regulator (AIRE) locus is associated with autoimmune Addison’s disease in Sweden
- 2018
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 8:1
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Tidskriftsartikel (refereegranskat)abstract
- Autoimmune Addison's disease (AAD) is the predominating cause of primary adrenal failure. Despite its high heritability, the rarity of disease has long made candidate-gene studies the only feasible methodology for genetic studies. Here we conducted a comprehensive reinvestigation of suggested AAD risk loci and more than 1800 candidate genes with associated regulatory elements in 479 patients with AAD and 2394 controls. Our analysis enabled us to replicate many risk variants, but several other previously suggested risk variants failed confirmation. By exploring the full set of 1800 candidate genes, we further identified common variation in the autoimmune regulator (AIRE) as a novel risk locus associated to sporadic AAD in our study. Our findings not only confirm that multiple loci are associated with disease risk, but also show to what extent the multiple risk loci jointly associate to AAD. In total, risk loci discovered to date only explain about 7% of variance in liability to AAD in our study population.
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| 2. |
- Eriksson, D, et al.
(författare)
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Extended exome sequencing identifies BACH2 as a novel major risk locus for Addison's disease
- 2016
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 286:6, s. 595-608
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Autoimmune disease is one of the leading causes of morbidity and mortality worldwide. In Addison's disease, the adrenal glands are targeted by destructive autoimmunity. Despite being the most common cause of primary adrenal failure, little is known about its aetiology.METHODS: To understand the genetic background of Addison's disease, we utilized the extensively characterized patients of the Swedish Addison Registry. We developed an extended exome capture array comprising a selected set of 1853 genes and their potential regulatory elements, for the purpose of sequencing 479 patients with Addison's disease and 1394 controls.RESULTS: We identified BACH2 (rs62408233-A, OR = 2.01 (1.71-2.37), P = 1.66 × 10(-15) , MAF 0.46/0.29 in cases/controls) as a novel gene associated with Addison's disease development. We also confirmed the previously known associations with the HLA complex.CONCLUSION: Whilst BACH2 has been previously reported to associate with organ-specific autoimmune diseases co-inherited with Addison's disease, we have identified BACH2 as a major risk locus in Addison's disease, independent of concomitant autoimmune diseases. Our results may enable future research towards preventive disease treatment.
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| 3. |
- Lundtoft, Christian, et al.
(författare)
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Relation between HLA and copy number variation of steroid 21-hydroxylase in a Swedish cohort of patients with autoimmune Addison's disease.
- 2023
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Ingår i: European journal of endocrinology. - : Bioscientifica. - 1479-683X .- 0804-4643. ; 189:2, s. 235-241
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Tidskriftsartikel (refereegranskat)abstract
- Autoantibodies against the adrenal enzyme 21-hydroxylase is a hallmark manifestation in autoimmune Addison's disease (AAD). Steroid 21-hydroxylase is encoded by CYP21A2, which is located in the human leucocyte antigen (HLA) region together with the highly similar pseudogene CYP21A1P. A high level of copy number variation is seen for the 2 genes, and therefore, we asked whether genetic variation of the CYP21 genes is associated with AAD.Case-control study on patients with AAD and healthy controls.Using next-generation DNA sequencing, we estimated the copy number of CYP21A2 and CYP21A1P, together with HLA alleles, in 479 Swedish patients with AAD and autoantibodies against 21-hydroxylase and in 1393 healthy controls.With 95% of individuals carrying 2 functional 21-hydroxylase genes, no difference in CYP21A2 copy number was found when comparing patients and controls. In contrast, we discovered a lower copy number of the pseudogene CYP21A1P among AAD patients (P = 5 × 10-44), together with associations of additional nucleotide variants, in the CYP21 region. However, the strongest association was found for HLA-DQB1*02:01 (P = 9 × 10-63), which, in combination with the DRB1*04:04-DQB1*03:02 haplotype, imposed the greatest risk of AAD.We identified strong associations between copy number variants in the CYP21 region and risk of AAD, although these associations most likely are due to linkage disequilibrium with disease-associated HLA class II alleles.
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| 4. |
- Bergman, Åke, et al.
(författare)
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Science and policy on endocrine disrupters must not be mixed : a reply to a "common sense" intervention by toxicology journal editors
- 2013
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Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- The "common sense" intervention by toxicology journal editors regarding proposed European Union endocrine disrupter regulations ignores scientific evidence and well-established principles of chemical risk assessment. In this commentary, endocrine disrupter experts express their concerns about a recently published, and is in our considered opinion inaccurate and factually incorrect, editorial that has appeared in several journals in toxicology. Some of the shortcomings of the editorial are discussed in detail. We call for a better founded scientific debate which may help to overcome a polarisation of views detrimental to reaching a consensus about scientific foundations for endocrine disrupter regulation in the EU.
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| 5. |
- Marklinder, Ingela, 1959-, et al.
(författare)
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A Structural Equation Model Demonstrating the Relationship between Food Safety Background, Knowledge, Attitudes and Behaviour among Swedish Students
- 2022
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Ingår i: Foods. - : MDPI. - 2304-8158. ; 11:11
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Tidskriftsartikel (refereegranskat)abstract
- Traditionally, food safety knowledge has been seen as a factor in improving food safety behaviour. However, the relationship between knowledge and behavior is complex. The aim of the present study was to investigate self-reported data from 408 university students regarding food safety background, knowledge, attitudes, and behaviour using Structural Equation Model (SEM) to examine the influence of different factors on food safety behaviour. The SEM was applied to four factors derived from the data: Background, Knowledge, Attitude and Behaviour. The novelty of this current investigation is the inclusion of the Background factor (genus; experience of cooking and handling different food items; experience of a food safety education course; the foremost sources of food safety knowledge). The factors were constructed from variables with sufficient factor loadings and set up in a predetermined structure confirmed to be valid in previous studies. The results, demonstrated as regression coefficients between factors, confirm that the Background factor strongly influenced Knowledge (0.842). The Knowledge factor, in turn, strongly affected Attitude (0.605), while it did not directly affect Behaviour (0.301) in the same way as Attitude. Attitude had a stronger influence on Behaviour (0.438) than Knowledge. Thus, the Attitude factor seemed to play a mediating role between Knowledge and Behaviour. This indicates that students ' attitudes towards the importance of food safety may have an impact on their food safety behavior, which should have implications for the development of food safety education. This warrants further investigation and practical development.
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| 6. |
- Marklinder, Ingela, 1959-, et al.
(författare)
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Food safety knowledge, sources thereof and self-reported behaviour among university students in Sweden
- 2020
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Ingår i: Food Control. - : Elsevier. - 0956-7135 .- 1873-7129. ; 113
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Tidskriftsartikel (refereegranskat)abstract
- International studies have noted shortcomings in food safety knowledge and behaviour among university students. In general students do not constitute a pronounced risk group but there are wider implications. In a foreseeable future some of them will become pregnant and a majority will be responsible for vulnerable groups in their near environment. A crucial question exists, therefore, about their food safety knowledge and safe food handling practices.The aim of this study is to investigate food safety knowledge, sources thereof and self-reported food safety behavior among university students in Sweden.A quantitative study design using a web-based questionnaire was chosen as the data collection method. The questionnaire was distributed through social media and e-mail.Among the 606 respondents from 24 Swedish universities 80% were 18-30 years and 78% were women. The average number of correct answers on the knowledge questions was 7.61 out of 12 (63.4%). The foremost source of food safety knowledge was "Family and friends" (45%). Just 21.1% reported Food safety education as a source, although 35.6% had experience of a course in food hygiene/safety and/or microbiology. Respondents who reported "Family and friends" to be the foremost food safety source of knowledge also got a significantly lower rate of correct answers. Students who estimated their food safety knowledge to be good also had more correct answers. Experience of food safety education at secondary school/university/working place/polytechnic school significantly correlated with more correct answers on the knowledge questions and indicated a safer self-reported behaviour. Those with fewer correct answers also reported more unfavourable behaviours. The present study indicates that education promotes more optimal behaviors. The authors would suggest a more systematic food safety education at younger ages.
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| 7. |
- Fall, Tove, et al.
(författare)
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Early Exposure to Dogs and Farm Animals and the Risk of Childhood Asthma
- 2015
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Ingår i: JAMA pediatrics. - Stockholm : American Medical Association. - 2168-6203 .- 2168-6211. ; 169:11
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE: The association between early exposure to animals and childhood asthma is not clear, and previous studies have yielded contradictory results.OBJECTIVE: To determine whether exposure to dogs and farm animals confers a risk of asthma.DESIGN, SETTING AND PARTICIPANTS: In a nationwide cohort study, the association between early exposure to dogs and farm animals and the risk of asthma was evaluated and included all children born in Sweden from January 1, 2001, to December 31, 2010 (N = 1 011 051), using registry data on dog and farm registration, asthma medication, diagnosis, and confounders for parents and their children. The association was assessed as the odds ratio (OR) for a current diagnosis of asthma at age 6 years for school-aged children and as the hazard ratio (HR) for incident asthma at ages 1 to 5 years for preschool-aged children. Data were analyzed from January 1, 2007, to September 30, 2012.EXPOSURES: Living with a dog or farm animal.MAIN OUTCOMES AND MEASURES: Childhood asthma diagnosis and medication used.RESULTS: Of the 1 011 051 children born during the study period, 376 638 preschool-aged (53 460 [14.2%] exposed to dogs and 1729 [0.5%] exposed to farm animals) and 276 298 school-aged children (22 629 [8.2%] exposed to dogs and 958 [0.3%] exposed to farm animals) were included in the analyses. Of these, 18 799 children (5.0%) in the preschool-aged children's cohort experienced an asthmatic event before baseline, and 28 511 cases of asthma and 906 071 years at risk were recorded during follow-up (incidence rate, 3.1 cases per 1000 years at risk). In the school-aged children's cohort, 11 585 children (4.2%) experienced an asthmatic event during the seventh year of life. Dog exposure during the first year of life was associated with a decreased risk of asthma in school-aged children (OR, 0.87; 95% CI, 0.81-0.93) and in preschool-aged children 3 years or older (HR, 0.90; 95% CI, 0.83-0.99) but not in children younger than 3 years (HR, 1.03; 95% CI, 1.00-1.07). Results were comparable when analyzing only first-born children. Farm animal exposure was associated with a reduced risk of asthma in both school-aged children and preschool-aged children (OR, 0.48; 95% CI, 0.31-0.76, and HR, 0.69; 95% CI, 0.56-0.84), respectively.CONCLUSIONS AND RELEVANCE: In this study, the data support the hypothesis that exposure to dogs and farm animals during the first year of life reduces the risk of asthma in children at age 6 years. This information might be helpful in decision making for families and physicians on the appropriateness and timing of early animal exposure.
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| 8. |
- Dulio, Valeria, et al.
(författare)
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The NORMAN Association and the European Partnership for Chemicals Risk Assessment (PARC) : let’s cooperate!
- 2020
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Ingår i: Environmental Sciences Europe. - : Springer. - 2190-4707 .- 2190-4715. ; 32:1
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Tidskriftsartikel (refereegranskat)abstract
- The Partnership for Chemicals Risk Assessment (PARC) is currently under development as a joint research and innovation programme to strengthen the scientific basis for chemical risk assessment in the EU. The plan is to bring chemical risk assessors and managers together with scientists to accelerate method development and the production of necessary data and knowledge, and to facilitate the transition to next-generation evidence-based risk assessment, a non-toxic environment and the European Green Deal. The NORMAN Network is an independent, well-established and competent network of more than 80 organisations in the field of emerging substances and has enormous potential to contribute to the implementation of the PARC partnership. NORMAN stands ready to provide expert advice to PARC, drawing on its long experience in the development, harmonisation and testing of advanced tools in relation to chemicals of emerging concern and in support of a European Early Warning System to unravel the risks of contaminants of emerging concern (CECs) and close the gap between research and innovation and regulatory processes. In this commentary we highlight the tools developed by NORMAN that we consider most relevant to supporting the PARC initiative: (i) joint data space and cutting-edge research tools for risk assessment of contaminants of emerging concern; (ii) collaborative European framework to improve data quality and comparability; (iii) advanced data analysis tools for a European early warning system and (iv) support to national and European chemical risk assessment thanks to harnessing, combining and sharing evidence and expertise on CECs. By combining the extensive knowledge and experience of the NORMAN network with the financial and policy-related strengths of the PARC initiative, a large step towards the goal of a non-toxic environment can be taken.
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| 9. |
- Liang, Yuli, 1985-, et al.
(författare)
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On estimation in hierarchical models with block circular covariance structures
- 2015
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Ingår i: Annals of the Institute of Statistical Mathematics. - : Springer. - 0020-3157 .- 1572-9052. ; 67:4, s. 773-791
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Tidskriftsartikel (refereegranskat)abstract
- Hierarchical linear models with a block circular covariance structure are considered. Sufficient conditions for obtaining explicit and unique estimators for the variance-covariance components are derived. Different restricted models are discussed and maximum likelihood estimators are presented. The theory is illustrated through covariance matrices of small sizes and a real-life example.
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| 10. |
- Liang, Yuli, 1985-, et al.
(författare)
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On properties of Toeplitz-type covariance matrices in models with nested random effects
- 2021
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Ingår i: Statistical papers. - : Springer. - 0932-5026 .- 1613-9798. ; 62:6, s. 2509-2528
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Tidskriftsartikel (refereegranskat)abstract
- Models that capture symmetries present in the data have been widely used in different applications, with early examples from psychometric and medical research. The aim of this article is to study a random effects model focusing on the covariance structure that is block circular symmetric. Useful results are obtained for the spectra of these structured matrices.
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