| 1. |
- Wessel, Jennifer, et al.
(författare)
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Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF = 1.4%) with lower FG (beta = -0.09 +/- 0.01 mmol l(-1), P = 3.4 x 10(-12)), T2D risk (OR[95% CI] = 0.86[0.76-0.96], P = 0.010), early insulin secretion (beta = -0.07 +/- 0.035 pmol(insulin) mmol(glucose)(-1), P = 0.048), but higher 2-h glucose (beta = 0.16 +/- 0.05 mmol l(-1), P = 4.3 x 10(-4)). We identify a gene-based association with FG at G6PC2 (p(SKAT) = 6.8 x 10(-6)) driven by four rare protein-coding SNVs (H177Y, Y207S, R283X and S324P). We identify rs651007 (MAF = 20%) in the first intron of ABO at the putative promoter of an antisense lncRNA, associating with higher FG (beta = 0.02 +/- 0.004 mmol l(-1), P = 1.3 x 10(-8)). Our approach identifies novel coding variant associations and extends the allelic spectrum of variation underlying diabetes-related quantitative traits and T2D susceptibility.
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| 2. |
- Andrén Aronsson, Carin, et al.
(författare)
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25(OH)D Levels in Infancy Is Associated With Celiac Disease Autoimmunity in At-Risk Children : A Case–Control Study
- 2021
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Ingår i: Frontiers in nutrition. - : Frontiers Media SA. - 2296-861X. ; 8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: An observed variation in the risk of celiac disease, according to the season of birth, suggests that vitamin D may affect the development of the disease. The aim of this study was to investigate if vitamin D concentration is associated with the risk of celiac disease autoimmunity (CDA) in genetically at-risk children. Study Design: Children prospectively followed in the multinational The Environmental Determinants of Diabetes in the Young study, conducted at six centers in Europe and the US, were selected for a 1-to-3 nested case–control study. In total, 281 case–control sets were identified. CDA was defined as positivity for tissue transglutaminase autoantibodies (tTGA) on two or more consecutive visits. Vitamin D was measured as 25-hydroxyvitamin D [25(OH)D] concentrations in all plasma samples prior to, and including, the first tTGA positive visit. Conditional logistic regression was used to examine the association between 25(OH)D and risk of CDA. Results: No significant association was seen between 25(OH)D concentrations (per 5 nmol/L increase) and risk for CDA development during early infancy (odds ratio [OR] 0.99, 95% confidence interval [CI] 0.95–1.04) or childhood (OR 1.02, 95% CI 0.97–1.07). When categorizing 25(OH)D concentrations, there was an increased risk of CDA with 25(OH)D concentrations <30 nmol/L (OR 2.23, 95% CI 1.29, 3.84) and >75 nmol/L (OR 2.10, 95% CI 1.28–3.44) in early infancy, as compared with 50–75 nmol/L. Conclusion: This study indicates that 25(OH)D concentrations <30 nmol/L and >75 nmol/L during early infancy were associated with an increased risk of developing CDA in genetically at-risk children. The non-linear relationship raises the need for more studies on the possible role of 25(OH)D in the relation to celiac disease onset.
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| 3. |
- Andrén Aronsson, Carin, et al.
(författare)
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Age at first introduction to complementary foods is associated with sociodemographic factors in children with increased genetic risk of developing type 1 diabetes.
- 2015
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Ingår i: Maternal and Child Nutrition. - : Wiley. - 1740-8709 .- 1740-8695. ; 11:4, s. 803-814
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Tidskriftsartikel (refereegranskat)abstract
- Infant's age at introduction to certain complementary foods (CF) has in previous studies been associated with islet autoimmunity, which is an early marker for type 1 diabetes (T1D). Various maternal sociodemographic factors have been found to be associated with early introduction to CF. The aims of this study were to describe early infant feeding and identify sociodemographic factors associated with early introduction to CF in a multinational cohort of infants with an increased genetic risk for T1D. The Environmental Determinants of Diabetes in the Young study is a prospective longitudinal birth cohort study. Infants (N = 6404) screened for T1D high risk human leucocyte antigen-DQ genotypes (DR3/4, DR4/4, DR4/8, DR3/3, DR4/4, DR4/1, DR4/13, DR4/9 and DR3/9) were followed for 2 years at six clinical research centres: three in the United States (Colorado, Georgia/Florida, Washington) and three in Europe (Sweden, Finland, Germany). Age at first introduction to any food was reported at clinical visits every third month from the age of 3 months. Maternal sociodemographic data were self-reported through questionnaires. Age at first introduction to CF was primarily associated with country of residence. Root vegetables and fruits were usually the first CF introduced in Finland and Sweden and cereals were usually the first CF introduced in the United States. Between 15% and 20% of the infants were introduced to solid foods before the age of 4 months. Young maternal age (<25 years), low educational level (<12 years) and smoking during pregnancy were significant predictors of early introduction to CF in this cohort. Infants with a relative with T1D were more likely to be introduced to CF later.
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| 4. |
- 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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| 5. |
- 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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| 6. |
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| 7. |
- Andrén Aronsson, Carin, et al.
(författare)
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Use of dietary supplements in pregnant women in relation to sociodemographic factors - a report from The Environmental Determinants of Diabetes in the Young (TEDDY) study.
- 2013
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Ingår i: Public Health Nutrition. - 1475-2727. ; 16:8, s. 1390-1402
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of the present study was to examine the prevalence and associated factors of dietary supplement use, particularly supplements containing vitamin D and fatty acids, in pregnant women enrolled in a multi-national study. DESIGN: The Environmental Determinants of Diabetes in the Young (TEDDY) study is a prospective longitudinal cohort study. Maternal dietary supplement use was self-reported through questionnaires at month 3 to 4 postpartum. SETTING: Six clinical research centres; three in the USA (Colorado, Georgia/Florida and Washington) and three in Europe (Sweden, Finland and Germany). SUBJECTS: Mothers (n 7326) to infants screened for high-risk HLA-DQ genotypes of type 1 diabetes. RESULTS: Ninety-two per cent of the 7326 women used one or more types of supplement during pregnancy. Vitamin D supplements were taken by 65 % of the women, with the highest proportion of users in the USA (80·5 %). Overall, 16 % of the women reported taking fatty acid supplements and a growing trend was seen in all countries between 2004 and 2010 (P < 0·0001). The use was more common in Germany (32 %) and the USA (24 %) compared with Finland (8·5 %) and Sweden (7·0 %). Being pregnant with the first child was a strong predictor for any supplement use in all countries. Low maternal age (<25 years), higher education, BMI ≥ 25·0 kg/m2 and smoking during pregnancy were factors associated with supplement use in some but not all countries. CONCLUSIONS: The majority of the women used dietary supplements during pregnancy. The use was associated with sociodemographic and behavioural factors, such as parity, maternal age, education, BMI and maternal smoking.
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| 8. |
- Aronsson, Carin Andrén, et al.
(författare)
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Dietary Intake and Body Mass Index Influence the Risk of Islet Autoimmunity in Genetically At-Risk Children : A Mediation Analysis Using the TEDDY Cohort
- 2023
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 2023
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Tidskriftsartikel (refereegranskat)abstract
- Background/Objective: Growth and obesity have been associated with increased risk of islet autoimmunity (IA) and progression to type 1 diabetes. We aimed to estimate the effect of energy-yielding macronutrient intake on the development of IA through BMI. Research Design and Methods: Genetically at-risk children (n = 5,084) in Finland, Germany, Sweden, and the USA, who were autoantibody negative at 2 years of age, were followed to the age of 8 years, with anthropometric measurements and 3-day food records collected biannually. Of these, 495 (9.7%) children developed IA. Mediation analysis for time-varying covariates (BMI z-score) and exposure (energy intake) was conducted. Cox proportional hazard method was used in sensitivity analysis. Results: We found an indirect effect of total energy intake (estimates: indirect effect 0.13 [0.05, 0.21]) and energy from protein (estimates: indirect effect 0.06 [0.02, 0.11]), fat (estimates: indirect effect 0.03 [0.01, 0.05]), and carbohydrates (estimates: indirect effect 0.02 [0.00, 0.04]) (kcal/day) on the development of IA. A direct effect was found for protein, expressed both as kcal/day (estimates: direct effect 1.09 [0.35, 1.56]) and energy percentage (estimates: direct effect 72.8 [3.0, 98.0]) and the development of GAD autoantibodies (GADA). In the sensitivity analysis, energy from protein (kcal/day) was associated with increased risk for GADA, hazard ratio 1.24 (95% CI: 1.09, 1.53), p = 0.042. Conclusions: This study confirms that higher total energy intake is associated with higher BMI, which leads to higher risk of the development of IA. A diet with larger proportion of energy from protein has a direct effect on the development of GADA.
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| 9. |
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| 10. |
- Beyerlein, Andreas, et al.
(författare)
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Intake of Energy and Protein is Associated with Overweight Risk at Age 5.5 Years : Results from the Prospective TEDDY Study
- 2017
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Ingår i: Obesity. - : Wiley. - 1930-7381. ; 25:8, s. 1435-1441
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The associations of energy, protein, carbohydrate, and fat intake with weight status up to the age of 5.5 years were prospectively assessed in The Environmental Determinants of Diabetes in the Young (TEDDY) study. Methods: Food record data (over 3 days) and BMI measurements between 0.25 and 5.5 years were available from 5,563 children with an increased genetic risk for type 1 diabetes followed from shortly after birth. Odds ratios (ORs) were calculated for overweight and obesity by previous intake of energy, protein, carbohydrate, and fat with adjustment for potential confounders. Results: Having overweight or obesity at the age of 5.5 years was positively associated with mean energy intake in previous age intervals (e.g., adjusted OR [95% CI] for overweight: 1.06 [1.04-1.09] per 100 kcal intake at the age of 4.5-5.0 years) and with protein intake after the age of 3.5 and 4.5 years, respectively (e.g., adjusted OR for overweight: 1.06 [1.03-1.09] per 1% of energy intake at the age of 4.5-5.0 years). The respective associations with carbohydrate and fat intake were less consistent. Conclusions: These findings indicate that energy and protein intake are positively associated with increased risk for overweight in childhood but yield no evidence for potential programming effects of protein intake in infancy.
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