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| 2. |
- Kim, Kwangwoo, et al.
(författare)
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High-density genotyping of immune loci in Koreans and Europeans identifies eight new rheumatoid arthritis risk loci
- 2015
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 74:3
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Tidskriftsartikel (refereegranskat)abstract
- Objective A highly polygenic aetiology and high degree of allele-sharing between ancestries have been well elucidated in genetic studies of rheumatoid arthritis. Recently, the high-density genotyping array Immunochip for immune disease loci identified 14 new rheumatoid arthritis risk loci among individuals of European ancestry. Here, we aimed to identify new rheumatoid arthritis risk loci using Korean-specific Immunochip data. Methods We analysed Korean rheumatoid arthritis case-control samples using the Immunochip and genome-wide association studies (GWAS) array to search for new risk alleles of rheumatoid arthritis with anticitrullinated peptide antibodies. To increase power, we performed a meta-analysis of Korean data with previously published European Immunochip and GWAS data for a total sample size of 9299 Korean and 45 790 European case-control samples. Results We identified eight new rheumatoid arthritis susceptibility loci (TNFSF4, LBH, EOMES, ETS1-FLI1, COG6, RAD51B, UBASH3A and SYNGR1) that passed a genome-wide significance threshold (p<5x10(-8)), with evidence for three independent risk alleles at 1q25/TNFSF4. The risk alleles from the seven new loci except for the TNFSF4 locus (monomorphic in Koreans), together with risk alleles from previously established RA risk loci, exhibited a high correlation of effect sizes between ancestries. Further, we refined the number of single nucleotide polymorphisms (SNPs) that represent potentially causal variants through a trans-ethnic comparison of densely genotyped SNPs. Conclusions This study demonstrates the advantage of dense-mapping and trans-ancestral analysis for identification of potentially causal SNPs. In addition, our findings support the importance of T cells in the pathogenesis and the fact of frequent overlap of risk loci among diverse autoimmune diseases.
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| 3. |
- Kim, Hye-Jin, et al.
(författare)
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Diffusible hydrogen behavior and delayed fracture of cold rolled martensitic steel in consideration of automotive manufacturing process and vehicle service environment
- 2020
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Ingår i: Journal of Materials Research and Technology. - : Elsevier Editora Ltda. - 2238-7854 .- 2214-0697. ; 9:6, s. 13483-13501
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Tidskriftsartikel (refereegranskat)abstract
- This study aims to elucidate the behavior of diffusible hydrogen and delayed fracture in martensitic steel with 1500 MPa strength during automotive painting process and under vehicle service conditions. A sequential process of automotive pretreatment line and vehicle service environment is simulated to evaluate the hydrogen pick up in each process. In case of the automotive painting line, the absorption of hydrogen is within the common range in the process of phosphating treatment and electrodeposition. The baking process plays an effective role for desorbing the diffusible hydrogen absorbed during the automotive pre-treatment such as zinc-phosphating, and electrodeposition process. In case of the corrosion environment under the automotive driving conditions, hydrogen induced delayed fracture is accelerated as the exposure time increases. Further, it is clarified that severe plastic deformation are the significant factors for hydrogen induced delayed fracture under with low pH value and present of chloride ion in a chemical solution parameter. In summary, hydrogen is transported constantly during electrodeposition sequential line process of automobile manufacturing below the hydrogen content of 0.5 ppm, which is not critical value for leading to hydrogen delayed fracture based on results of slow strain rate tensile tests. However, exposure to extreme conditions under service environment of vehicle, such as acidic solution and chloride chemistry solution that result in high level of hydrogen absorption, severe plastic deformation in the sheared edge, and constantly applied internal or external stresses, can cause the hydrogen induced delayed fracture in the fully martensitic steels. © 2020 The Authors
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| 4. |
- Agardh, Daniel, et al.
(författare)
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Clinical Features of Celiac Disease: A Prospective Birth Cohort.
- 2015
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:4, s. 627-634
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Tidskriftsartikel (refereegranskat)abstract
- To investigate clinical features of celiac disease (CD) and their association with risk factors for CD in a genetic risk birth cohort.
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| 5. |
- Andrén Aronsson, Carin, et al.
(författare)
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Age at Gluten Introduction and Risk of Celiac Disease.
- 2015
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 135:2, s. 239-245
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Tidskriftsartikel (refereegranskat)abstract
- The goal of this study was to determine whether age at introduction to gluten was associated with risk for celiac disease (CD) in genetically predisposed children.
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| 6. |
- Andrén Aronsson, Carin, et al.
(författare)
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Association of gluten intake during the first 5 years of life with incidence of celiac disease autoimmunity and celiac disease among children at increased risk
- 2019
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Ingår i: JAMA - Journal of the American Medical Association. - : American Medical Association (AMA). - 0098-7484. ; 322:6, s. 514-523
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Tidskriftsartikel (refereegranskat)abstract
- Importance: High gluten intake during childhood may confer risk of celiac disease. Objectives: To investigate if the amount of gluten intake is associated with celiac disease autoimmunity and celiac disease in genetically at-risk children. Design, Setting, and Participants: The participants in The Environmental Determinants of Diabetes in the Young (TEDDY), a prospective observational birth cohort study designed to identify environmental triggers of type 1 diabetes and celiac disease, were followed up at 6 clinical centers in Finland, Germany, Sweden, and the United States. Between 2004 and 2010, 8676 newborns carrying HLA antigen genotypes associated with type 1 diabetes and celiac disease were enrolled. Screening for celiac disease with tissue transglutaminase autoantibodies was performed annually in 6757 children from the age of 2 years. Data on gluten intake were available in 6605 children (98%) by September 30, 2017. Exposures: Gluten intake was estimated from 3-day food records collected at ages 6, 9, and 12 months and biannually thereafter until the age of 5 years. Main Outcomes and Measures: The primary outcome was celiac disease autoimmunity, defined as positive tissue transglutaminase autoantibodies found in 2 consecutive serum samples. The secondary outcome was celiac disease confirmed by intestinal biopsy or persistently high tissue transglutaminase autoantibody levels. Results: Of the 6605 children (49% females; median follow-up: 9.0 years [interquartile range, 8.0-10.0 years]), 1216 (18%) developed celiac disease autoimmunity and 447 (7%) developed celiac disease. The incidence for both outcomes peaked at the age of 2 to 3 years. Daily gluten intake was associated with higher risk of celiac disease autoimmunity for every 1-g/d increase in gluten consumption (hazard ratio [HR], 1.30 [95% CI, 1.22-1.38]; absolute risk by the age of 3 years if the reference amount of gluten was consumed, 28.1%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 34.2%; absolute risk difference, 6.1% [95% CI, 4.5%-7.7%]). Daily gluten intake was associated with higher risk of celiac disease for every 1-g/d increase in gluten consumption (HR, 1.50 [95% CI, 1.35-1.66]; absolute risk by age of 3 years if the reference amount of gluten was consumed, 20.7%; absolute risk if gluten intake was 1-g/d higher than the reference amount, 27.9%; absolute risk difference, 7.2% [95% CI, 6.1%-8.3%]). Conclusions and Relevance: Higher gluten intake during the first 5 years of life was associated with increased risk of celiac disease autoimmunity and celiac disease among genetically predisposed children.
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| 7. |
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| 8. |
- Haghighi, Mona, et al.
(författare)
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A Comparison of Rule-based Analysis with Regression Methods in Understanding the Risk Factors for Study Withdrawal in a Pediatric Study
- 2016
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Regression models are extensively used in many epidemiological studies to understand the linkage between specific outcomes of interest and their risk factors. However, regression models in general examine the average effects of the risk factors and ignore subgroups with different risk profiles. As a result, interventions are often geared towards the average member of the population, without consideration of the special health needs of different subgroups within the population. This paper demonstrates the value of using rule-based analysis methods that can identify subgroups with heterogeneous risk profiles in a population without imposing assumptions on the subgroups or method. The rules define the risk pattern of subsets of individuals by not only considering the interactions between the risk factors but also their ranges. We compared the rule-based analysis results with the results from a logistic regression model in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Both methods detected a similar suite of risk factors, but the rule-based analysis was superior at detecting multiple interactions between the risk factors that characterize the subgroups. A further investigation of the particular characteristics of each subgroup may detect the special health needs of the subgroup and lead to tailored interventions.
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| 9. |
- Hagopian, William, et al.
(författare)
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Co-occurrence of Type 1 Diabetes and Celiac Disease Autoimmunity
- 2017
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 140:5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND AND OBJECTIVES: Few birth cohorts have prospectively followed development of type 1 diabetes (T1D) and celiac disease (CD) autoimmunities to determine timing, extent of co-occurrence, and associated genetic and demographic factors.METHODS: In this prospective birth cohort study, 8676 children at high genetic risk of both diseases were enrolled and 5891 analyzed in median follow-up of 66 months. Along with demographic factors and HLA-DR-DQ, genotypes for HLA-DPB1 and 5 non-HLA loci conferring risk of both T1D and CD were analyzed.RESULTS: Development of persistent islet autoantibodies (IAs) and tissue transglutaminase autoantibodies (tTGAs), as well as each clinical disease, was evaluated quarterly from 3 to 48 months of age and semiannually thereafter. IAs alone appeared in 367, tTGAs alone in 808, and both in 90 children. Co-occurrence significantly exceeded the expected rate. IAs usually, but not always, appeared earlier than tTGAs. IAs preceding tTGAs was associated with increasing risk of tTGAs (hazard ratio [HR]: 1.48; 95% confidence interval [CI]: 1.15-1.91). After adjusting for country, sex, family history, and all other genetic loci, significantly greater co-occurrence was observed in children with a T1D family history (HR: 2.80), HLA-DR3/4 (HR: 1.94) and single-nucleotide polymorphism rs3184504 at SH2B3 (HR: 1.53). However, observed co-occurrence was not fully accounted for by all analyzed factors.CONCLUSIONS: In early childhood, T1D autoimmunity usually precedes CD autoimmunity. Preceding IAs significantly increases the risk of subsequent tTGAs. Co-occurrence is greater than explained by demographic factors and extensive genetic risk loci, indicating that shared environmental or pathophysiological mechanisms may contribute to the increased risk.
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| 10. |
- Hård af Segerstad, Elin M., et al.
(författare)
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Daily intake of milk powder and risk of celiac disease in early childhood : A nested case-control study
- 2018
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Ingår i: Nutrients. - : MDPI AG. - 2072-6643. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Milk powder and gluten are common components in Swedish infants’ diets. Whereas large intakes of gluten early in life increases the risk of celiac disease in genetically at-risk Swedish children, no study has yet evaluated if intake of milk powder by 2 years of age is associated with celiac disease. A 1-to-3 nested case-control study, comprised of 207 celiac disease children and 621 controls matched for sex, birth year, and HLA genotype, was performed on a birth cohort of HLA-DR3-DQ2 and/or DR4-DQ8-positive children. Subjects were screened annually for celiac disease using tissue transglutaminase autoantibodies (tTGA). Three-day food records estimated the mean intake of milk powder at ages 6 months, 9 months, 12 months, 18 months, and 24 months. Conditional logistic regression calculated odds ratios (OR) at last intake prior to seroconversion of tTGA positivity, and for each time-point respectively and adjusted for having a first-degree relative with celiac disease and gluten intake. Intake of milk powder prior to seroconversion of tTGA positivity was not associated with celiac disease (OR = 1.00; 95% CI = 0.99, 1.03; p = 0.763). In conclusion, intake of milk powder in early childhood is not associated with celiac disease in genetically susceptible children.
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