| 1. |
- Fragoso-Bargas, Nicolas, et al.
(författare)
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Cohort profile : Epigenetics in Pregnancy (EPIPREG) - population-based sample of European and South Asian pregnant women with epigenome-wide DNA methylation (850k) in peripheral blood leukocytes
- 2021
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Ingår i: PLoS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 16:8, s. 1-15
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancy is a valuable model to study the association between DNA methylation and several cardiometabolic traits, due to its direct potential to influence mother's and child's health. Epigenetics in Pregnancy (EPIPREG) is a population-based sample with the aim to study associations between DNA-methylation in pregnancy and cardiometabolic traits in South Asian and European pregnant women and their offspring. This cohort profile paper aims to present our sample with genetic and epigenetic data and invite researchers with similar cohorts to collaborative projects, such as replication of ours or their results and meta-analysis. In EPIPREG we have quantified epigenome-wide DNA methylation in maternal peripheral blood leukocytes in gestational week 28±1 in Europeans (n = 312) and South Asians (n = 168) that participated in the population-based cohort STORK Groruddalen, in Norway. DNA methylation was measured with Infinium MethylationEPIC BeadChip (850k sites), with technical validation of four CpG sites using bisulphite pyrosequencing in a subset (n = 30). The sample is well characterized with few missing data on e.g. genotype, universal screening for gestational diabetes, objectively measured physical activity, bioelectrical impedance, anthropometrics, biochemical measurements, and a biobank with maternal serum and plasma, urine, placenta tissue. In the offspring, we have repeated ultrasounds during pregnancy, cord blood, and anthropometrics up to 4 years of age. We have quantified DNA methylation in peripheral blood leukocytes in nearly all eligible women from the STORK Groruddalen study, to minimize the risk of selection bias. Genetic principal components distinctly separated Europeans and South Asian women, which fully corresponded with the self-reported ethnicity. Technical validation of 4 CpG sites from the methylation bead chip showed good agreement with bisulfite pyrosequencing. We plan to study associations between DNA methylation and cardiometabolic traits and outcomes.
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| 2. |
- Arora, Geeti P, et al.
(författare)
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Phenotypic and genotypic differences between Indian and Scandinavian women with gestational diabetes mellitus
- 2019
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Ingår i: Journal of Internal Medicine. - : Wiley. - 1365-2796 .- 0954-6820. ; 286:2, s. 192-206
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: Gestational diabetes mellitus (GDM) is a transient form of diabetes characterized by impaired insulin secretion and action during pregnancy. Population-based differences in prevalence exist which could be explained by phenotypic and genetic differences. The aim of this study was to examine these differences in pregnant women from Punjab, India and Scandinavia.METHODS: 85 GDM/T2D loci in European and/or Indian populations from previous studies were assessed for association with GDM based on Swedish GDM criteria in 4018 Punjabi Indian and 507 Swedish pregnant women. Selected loci were replicated in Scandinavian cohorts, Radiel (N=398, Finnish), STORK/STORK-G (N=780, Norwegian).RESULTS: Punjabi Indian women had higher GDM prevalence, lower insulin secretion and better insulin sensitivity than Swedish women. There were significant frequency differences of GDM/T2D risk alleles between both populations. rs7178572 at HMG20A, previously associated with GDM in South Indian and European women was replicated in North Indian women. The T2D risk SNP rs11605924 in the CRY2 gene was associated with increased GDM risk in Scandinavian but decreased risk in Punjabi Indian women. No other overlap was seen between GDM loci in both populations.CONCLUSIONS: GDM is more common in Indian than Swedish women, which partially can be attributed to differences in insulin secretion and action. There was marked heterogeneity in the GDM phenotypes between the populations which could only partially be explained by genetic differences. This article is protected by copyright. All rights reserved.
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| 3. |
- Birkeland, Kåre I., et al.
(författare)
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Heart failure and chronic kidney disease manifestation and mortality risk associations in type 2 diabetes : A large multinational cohort study
- 2020
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Ingår i: Diabetes, obesity and metabolism. - : John Wiley & Sons. - 1462-8902 .- 1463-1326. ; 22:9, s. 1607-1618
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Tidskriftsartikel (refereegranskat)abstract
- Aims To examine the manifestation of cardiovascular or renal disease (CVRD) in patients with type 2 diabetes (T2D) initially free from CVRD as well as the mortality risks associated with these diseases.Methods Patients free from CVRD were identified from healthcare records in England, Germany, Japan, the Netherlands, Norway and Sweden at a fixed date. CVRD manifestation was defined by first diagnosis of cardiorenal disease, or a stroke, myocardial infarction (MI) or peripheral artery disease (PAD) event. The mortality risk associated with single CVRD history of heart failure (HF), chronic kidney disease (CKD), MI, stroke or PAD was compared with that associated with CVRD-free status.Results Of 1 177 896 patients with T2D, 772 336 (66%) were CVRD-free and followed for a mean of 4.5 years. A total of 137 081 patients (18%) developed a first CVRD manifestation, represented by CKD (36%), HF (24%), stroke (16%), MI (14%) and PAD (10%). HF or CKD was associated with increased cardiovascular and all-cause mortality risk: hazard ratio (HR) 2.02 (95% confidence interval [CI] 1.75-2.33) and HR 2.05 (95% CI 1.82-2.32), respectively. HF and CKD were separately associated with significantly increased mortality risks, and the combination was associated with the highest cardiovascular and all-cause mortality risk: HRs 3.91 (95% CI 3.02-5.07) and 3.14 (95% CI 2.90-3.40), respectively.Conclusion In a large multinational study of >750 000 CVRD-free patients with T2D, HF and CKD were consistently the most frequent first cardiovascular disease manifestations and were also associated with increased mortality risks. These novel findings show these cardiorenal diseases to be important and serious complications requiring improved preventive strategies.
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| 4. |
- Fragoso-Bargas, Nicolas, et al.
(författare)
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Epigenome-wide association study of serum folate in maternal peripheral blood leukocytes
- 2023
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Ingår i: Epigenomics. - : Future Medicine Ltd. - 1750-192X .- 1750-1911. ; 15:1, s. 39-52
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To perform an epigenome-wide association study (EWAS) of serum folate in maternal blood. Methods: Cross-ancestry (Europeans = 302, South Asians = 161) and ancestry-specific EWAS in the EPIPREG cohort were performed, followed by methyl quantitative trait loci analysis and association with cardiometabolic phenotypes. Replication was attempted using maternal folate intake and blood methylation data from the MoBa study and verified if the findings were significant in a previous EWAS of maternal serum folate in cord blood. Results & conclusion: cg19888088 (cross-ancestry) in EBF3, cg01952260 (Europeans) and cg07077240 (South Asians) in HERC3 were associated with serum folate. cg19888088 and cg01952260 were associated with diastolic blood pressure. cg07077240 was associated with variants in CASC15. The findings were not replicated and were not significant in cord blood.
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| 5. |
- Gulseth, Hanne L., et al.
(författare)
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Dietary fat modifications and blood pressure in subjects with the metabolic syndrome in the LIPGENE dietary intervention study
- 2010
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Ingår i: British Journal of Nutrition. - 0007-1145 .- 1475-2662. ; 104:2, s. 160-163
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Tidskriftsartikel (refereegranskat)abstract
- Hypertension is a key feature of the metabolic syndrome. Lifestyle and dietary changes may affect blood pressure (BP), but the knowledge of the effects of dietary fat modification in subjects with the metabolic syndrome is limited. The objective of the present study was to investigate the effect of an isoenergetic change in the quantity and quality of dietary fat on BP in subjects with the metabolic syndrome. In a 12-week European multi-centre, parallel, randomised controlled dietary intervention trial (LIPGENE), 486 subjects were assigned to one of the four diets distinct in fat quantity and quality: two high-fat diets rich in saturated fat or monounsaturated fat and two low-fat, high-complex carbohydrate diets with or without 1.2 g/d of very long-chain n-3 PUFA supplementation. There were no overall differences in systolic BP (SBP), diastolic BP or pulse pressure (PP) between the dietary groups after the intervention. The high-fat diet rich in saturated fat had minor unfavourable effects on SBP and PP in males.
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| 6. |
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| 7. |
- Knudsen, Søren Tang, et al.
(författare)
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Risk factor management of type 2 diabetic patients in primary care in the Scandinavian countries between 2003 and 2015
- 2021
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Ingår i: Primary Care Diabetes. - : Elsevier BV. - 1751-9918 .- 1878-0210. ; 15:2, s. 262-268
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Tidskriftsartikel (refereegranskat)abstract
- Aims: To observe and report population demography, comorbidities, risk factor levels and risk factor treatment in a sample of individuals treated for type 2 diabetes in primary care in Norway, Sweden and Denmark. Methods: Retrospective observational cohort using extraction of data from electronic medical records linked with national health care registries. Results: Sixty primary care clinics participated with annual cross-sectional data (2003 to 2015). In 2015 the sample consisted of 31,632 individuals. Mean age (64.5–66.8 years) and proportion of women (43–45%) were similar. The prevalence of cardiovascular disease in 2015 was 40.7%, 41.6% and 38.0% for Norway, Sweden and Denmark, respectively and 84% to 89% of patients were receiving a pharmacological anti-diabetic treatment. More Danish patients reached targets for HbA1c and LDL cholesterol, while more patients in Sweden and Denmark met the blood pressure target of <130/80 mmHg as compared to Norway. Conclusions: In three comparable public primary health care systems we found a high prevalence of cardiovascular disease and differences in risk factor treatment and attainment of risk factor goals. With recent guideline changes there is potential for further prevention of diabetes complications in primary care in the future.
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| 8. |
- Linares-Pineda, Teresa M, et al.
(författare)
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DNA methylation risk score for type 2 diabetes is associated with gestational diabetes
- 2024
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Ingår i: Cardiovascular Diabetology. - 1475-2840. ; 23
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Gestational diabetes mellitus (GDM) and type 2 diabetes mellitus (T2DM) share many pathophysiological factors including genetics, but whether epigenetic marks are shared is unknown. We aimed to test whether a DNA methylation risk score (MRS) for T2DM was associated with GDM across ancestry and GDM criteria.METHODS: In two independent pregnancy cohorts, EPIPREG (n = 480) and EPIDG (n = 32), DNA methylation in peripheral blood leukocytes was measured at a gestational age of 28 ± 2. We constructed an MRS in EPIPREG and EPIDG based on CpG hits from a published epigenome-wide association study (EWAS) of T2DM.RESULTS: With mixed models logistic regression of EPIPREG and EPIDG, MRS for T2DM was associated with GDM: odd ratio (OR)[95% CI]: 1.3 [1.1-1.8], P = 0.002 for the unadjusted model, and 1.4 [1.1-1.7], P = 0.00014 for a model adjusted by age, pre-pregnant BMI, family history of diabetes and smoking status. Also, we found 6 CpGs through a meta-analysis (cg14020176, cg22650271, cg14870271, cg27243685, cg06378491, cg25130381) associated with GDM, and some of their methylation quantitative loci (mQTLs) were related to T2DM and GDM.CONCLUSION: For the first time, we show that DNA methylation marks for T2DM are also associated with GDM, suggesting shared epigenetic mechanisms between GDM and T2DM.
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| 9. |
- Moen, Gunn Helen, et al.
(författare)
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Epigenetic modifications and gestational diabetes : A Systematic review of published literature
- 2017
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Ingår i: European Journal of Endocrinology. - 0804-4643. ; 176:5, s. 247-267
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Forskningsöversikt (refereegranskat)abstract
- Objective: To summarize the current knowledge on epigenetic alterations in mother and offspring subjected to gestational diabetes (GDM) and indicate future topics for research. Design: Systematic review. Methods: We performed extensive searches in PubMed, EMBASE and Google scholar, using a combination of the search terms: GDM, gestational diabetes, epigenetic(s), methylation, histone modification, histone methylation, histone acetylation, microRNA and miRNA. Studies that compared women diagnosed with GDM and healthy controls were included. Two authors independently scanned the abstracts, and all included papers were read by at least two authors. The searches were completed on October 31st, 2016. Results: We identified 236 articles, of which 43 were considered relevant for this systematic review. Studies published showed that epigenetic alterations could be found in both mothers with GDM and their offspring. However, differences in methodology, diagnostic criteria for GDM and populations studied, together with a limited number of published studies and small sample sizes, preclude clear conclusions about the role of epigenetic modifications in transmitting risk from GDM mothers to their offspring. Conclusion: The current research literature suggests that GDM may have impact on epigenetic modifications in the mother and offspring. However, larger studies that include multiple cohorts of GDM patients and their offspring are needed.
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| 10. |
- Moen, Gunn Helen, et al.
(författare)
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Genetic determinants of glucose levels in pregnancy : Genetic risk scores analysis and GWAS in the Norwegian STORK cohort
- 2018
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Ingår i: European Journal of Endocrinology. - 0804-4643. ; 179:6, s. 363-372
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Tidskriftsartikel (refereegranskat)abstract
- Objective: Hyperglycaemia during pregnancy increases the risk of adverse health outcomes in mother and child, but the genetic aetiology is scarcely studied. Our aims were to (1) assess the overlapping genetic aetiology between the pregnant and non-pregnant population and (2) assess the importance of genome-wide polygenic contributions to glucose traits during pregnancy, by exploring whether genetic risk scores (GRSs) for fasting glucose (FG), 2-h glucose (2hG), type 2 diabetes (T2D) and BMI in non-pregnant individuals were associated with glucose measures in pregnant women. Methods: We genotyped 529 Norwegian pregnant women and constructed GRS from known genome-wide significant variants and SNPs weakly associated (p>5×10−8) with FG, 2hG, BMI and T2D from external genome-wide association studies (GWAS) and examined the association between these scores and glucose measures at gestational weeks 14-16 and 30-32. We also performed GWAS of FG, 2hG and shape information from the glucose curve during an oral glucose tolerance test (OGTT). Results: GRSFG explained similar variance during pregnancy as in the non-pregnant population (~5%). GRSBMI and GRST2D explained up to 1.3% of the variation in the glucose traits in pregnancy. If we included variants more weakly associated with these traits, GRS2hG and GRST2D explained up to 2.4% of the variation in the glucose traits in pregnancy, highlighting the importance of polygenic contributions. Conclusions: Our results suggest overlap in the genetic aetiology of FG in pregnant and non-pregnant individuals. This was less apparent with 2hG, suggesting potential differences in postprandial glucose metabolism inside and outside of pregnancy.
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