| 1. |
- van de Vegte, Yordi, et al.
(författare)
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Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
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| 2. |
- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 3. |
- Atun, Rifat, et al.
(författare)
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Sustainable care for children with cancer : a Lancet Oncology Commission
- 2020
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Ingår i: The Lancet Oncology. - 1470-2045. ; 21:4, s. 185-224
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Forskningsöversikt (refereegranskat)abstract
- We estimate that there will be 13·7 million new cases of childhood cancer globally between 2020 and 2050. At current levels of health system performance (including access and referral), 6·1 million (44·9%) of these children will be undiagnosed. Between 2020 and 2050, 11·1 million children will die from cancer if no additional investments are made to improve access to health-care services or childhood cancer treatment. Of this total, 9·3 million children (84·1%) will be in low-income and lower-middle-income countries. This burden could be vastly reduced with new funding to scale up cost-effective interventions. Simultaneous comprehensive scale-up of interventions could avert 6·2 million deaths in children with cancer in this period, more than half (56·1%) of the total number of deaths otherwise projected. Taking excess mortality risk into consideration, this reduction in the number of deaths is projected to produce a gain of 318 million life-years. In addition, the global lifetime productivity gains of US$2580 billion in 2020–50 would be four times greater than the cumulative treatment costs of $594 billion, producing a net benefit of $1986 billion on the global investment: a net return of $3 for every $1 invested. In sum, the burden of childhood cancer, which has been grossly underestimated in the past, can be effectively diminished to realise massive health and economic benefits and to avert millions of needless deaths.
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| 4. |
- Bergqvist-Norén, Linnea, et al.
(författare)
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Patterns and correlates of objectively measured physical activity in 3-year-old children
- 2020
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Ingår i: BMC Pediatrics. - : Springer Science and Business Media LLC. - 1471-2431. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To increase the knowledge about physical activity (PA) patterns and correlates among children under the age of 4, there is a need for study's using objective measurements. The aim of this study was therefore to investigate if objectively measured PA among 3-year-old children differed between day of week and time of day and whether it correlated to child weight status and sex as well as parental weight status and education.METHODS: Totally 61 children (51% girls) aged 3, participating in Early Stockholm Obesity Prevention Project were included. PA was measured with a tri-axial accelerometer (ActiGraph GT3X+) worn on the non-dominant wrist for one week. The main outcome was average PA expressed as counts per minute from the vector magnitude. PA and demographics/family-related factors were collected at baseline and at age 3. To analyze the results simple linear regression, ANOVA and paired t-tests were performed.RESULTS: The mean number of valid days was 6.7 per child. The children were more active on weekdays than weekends (p < 0.01) and the hourly pattern differed over the day with children being most active midmorning and midafternoon (p = 0.0001). Children to parents with low education were more active (p = 0.01) than those with highly educated parents. No differences in PA by child weight status, sex nor parental weight status were found.CONCLUSIONS: PA in 3-year-old children was lower during weekends than weekdays and varied over the day. Boys and girls had similar PA patterns, these patterns were independent of child or parental weight status. Children to parents with low education were more active than their counterparts. The fact that PA differed between weekdays and weekends indicates that PA might be affectable in 3-year-old children.
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| 5. |
- Carlsson, Annelie, et al.
(författare)
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Absence of Islet Autoantibodies and Modestly Raised Glucose Values at Diabetes Diagnosis Should Lead to Testing for MODY : Lessons From a 5-Year Pediatric Swedish National Cohort Study
- 2020
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Ingår i: Diabetes Care. - Arlington, VA, United States : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 43:1, s. 82-89
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE Identifying maturity-onset diabetes of the young (MODY) in pediatric populations close to diabetes diagnosis is difficult. Misdiagnosis and unnecessary insulin treatment are common. We aimed to identify the discriminatory clinical features at diabetes diagnosis of patients with glucokinase (GCK), hepatocyte nuclear factor-1A (HNF1A), and HNF4A MODY in the pediatric population.RESEARCH DESIGN AND METHODS Swedish patients (n = 3,933) aged 1–18 years, diagnosed with diabetes May 2005 to December 2010, were recruited from the national consecutive prospective cohort Better Diabetes Diagnosis. Clinical data, islet autoantibodies (GAD insulinoma antigen-2, zinc transporter 8, and insulin autoantibodies), HLA type, and C-peptide were collected at diagnosis. MODY was identified by sequencing GCK, HNF1A, and HNF4A, through either routine clinical or research testing.RESULTS The minimal prevalence of MODY was 1.2%. Discriminatory factors for MODY at diagnosis included four islet autoantibody negativity (100% vs. 11% not-known MODY; P = 2 × 10−44), HbA1c (7.0% vs. 10.7% [53 vs. 93 mmol/mol]; P = 1 × 10−20), plasma glucose (11.7 vs. 26.7 mmol/L; P = 3 × 10−19), parental diabetes (63% vs. 12%; P = 1 × 10−15), and diabetic ketoacidosis (0% vs. 15%; P = 0.001). Testing 303 autoantibody-negative patients identified 46 patients with MODY (detection rate 15%). Limiting testing to the 73 islet autoantibody-negative patients with HbA1c <7.5% (58 mmol/mol) at diagnosis identified 36 out of 46 (78%) patients with MODY (detection rate 49%). On follow-up, the 46 patients with MODY had excellent glycemic control, with an HbA1c of 6.4% (47 mmol/mol), with 42 out of 46 (91%) patients not on insulin treatment.CONCLUSIONS At diagnosis of pediatric diabetes, absence of all islet autoantibodies and modest hyperglycemia (HbA1c <7.5% [58 mmol/mol]) should result in testing for GCK, HNF1A, and HNF4A MODY. Testing all 12% patients negative for four islet autoantibodies is an effective strategy for not missing MODY but will result in a lower detection rate. Identifying MODY results in excellent long-term glycemic control without insulin.
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| 6. |
- de Groot, Frank M. F., et al.
(författare)
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2p x-ray absorption spectroscopy of 3d transition metal systems
- 2021
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Ingår i: Journal of Electron Spectroscopy and Related Phenomena. - : Elsevier BV. - 0368-2048 .- 1873-2526. ; 249
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Tidskriftsartikel (refereegranskat)abstract
- This review provides an overview of the different methods and computer codes that are used to interpret 2p x-ray absorption spectra of 3d transition metal ions. We first introduce the basic parameters and give an overview of the methods used. We start with the semi-empirical multiplet codes and compare the different codes that are available. A special chapter is devoted to the user friendly interfaces that have been written on the basis of these codes. Next we discuss the first principle codes based on band structure, including a chapter on Density Functional theory based approaches. We also give an overview of the first-principle multiplet codes that start from a cluster calculation and we discuss the wavefunction based methods, including multi-reference methods. We end the review with a discussion of the link between theory and experiment and discuss the open issues in the spectral analysis.
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| 7. |
- de las Fuentes, Lisa, et al.
(författare)
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Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci
- 2021
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Ingår i: Molecular Psychiatry. - : Springer Nature. - 1359-4184 .- 1476-5578. ; 26:6, s. 2111-2125
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Tidskriftsartikel (refereegranskat)abstract
- Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, “Some College” (yes/no) and “Graduated College” (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.
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| 8. |
- Ek, Anna E., et al.
(författare)
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Microalbuminuria and retinopathy in adolescents and young adults with type 1 and type 2 diabetes
- 2020
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Ingår i: Pediatric Diabetes. - : Hindawi Limited. - 1399-543X .- 1399-5448. ; 21:7, s. 1310-1321
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Tidskriftsartikel (refereegranskat)abstract
- Aim: To estimate the occurrence of complications related to early-onset type 2 diabetes compared with type 1 diabetes. Methods: All individuals registered in the Swedish Pediatric Quality Diabetes Register and the Swedish National Diabetes Register with type 2 diabetes diagnosis at 10 to 25 years of age between 1996 and 2014 (n = 1413) were included. As controls, individuals with type 1 diabetes were randomly selected from the same registers and were matched for age, sex, and year-of-onset (n = 3748). Results: Of the adolescents with type 2 diabetes in the pediatric register, 7.7% had microalbuminuria and 24.6% had signs of retinopathy 5 years after diagnosis, whereas the adolescents with type 1 diabetes 3.8% had microalbuminuria and 19.2% had retinopathy. Among the young adults with type 2 diabetes from the adult diabetes register 10 years after diagnosis 15.2% had microalbuminuria and 39.7% retinopathy, whereas the young adults with type 1 diabetes 4.8% had microalbuminuria and 43.8% retinopathy. After adjustment for established risk factors measured over time in the whole combined cohort, individuals with type 2 diabetes had significantly higher risk of microalbuminuria with a hazard ratio (HR) of 3.32 (95% confidence interval, CI 2.86-3.85, P <.001), and retinopathy with a HR of 1.17 (95% CI 1.06-1.30, P 0.04). Conclusions: The prevalence of complications and comorbidities was higher among those with type 2 diabetes compared with type 1 diabetes, although prevalent in both groups. Early monitoring and more active treatment of type 2 diabetes in young individuals is required.
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| 9. |
- Henfridsson, Pia, et al.
(författare)
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Long-term changes in dietary intake and its association with eating-related problems after gastric bypass in adolescents.
- 2022
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Ingår i: Surgery for obesity and related diseases : official journal of the American Society for Bariatric Surgery. - : Elsevier BV. - 1878-7533. ; 18:12, s. 1399-1406
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Tidskriftsartikel (refereegranskat)abstract
- Roux-en-Y gastric bypass (RYGB) surgery is an established, effective treatment for severe adolescent obesity. Long-term dietary intake and the relationship to eating-related problems are scarcely evaluated in this population.Assess changes in dietary intake in adolescents after RYGB and explore associations between dietary intake and eating-related problems.Multicenter study in Swedish university hospitals.Diet history, binge eating scale (BES), and Three-Factor Eating Questionnaire were assessed preoperatively and 1, 2, and 5 years after RYGB in 85 adolescents (67% female) aged 16.5 ± 1.2 years with a body mass index (BMI) of 45.5 ± 6.0 kg/m2 and compared with control individuals at 5 years.Five-year BMI change was -28.6% ± 12.7% versus +9.9% ± 18.9% in RYGB patients versus control individuals (P < .001). Through 5 years, RYGB adolescents reported reduced energy intake, portion size of cooked meals at dinner, and milk/yoghurt consumption (P < .01). The BES scores were 9.3 ± 8.3 versus 13.4 ± 10.5 in RYGB patients versus control individuals (P = .04). Association between BES score and energy intake was stronger in control individuals (r = .27 versus r = .62 in RYGB patients versus control individuals, P < .001). At 5 years, lower energy intake was associated with greater BMI loss in all adolescents (r = .33, P < .001). Higher scores in BES and uncontrolled and emotional eating were associated with higher energy intake, cooked meals, candies/chocolates, cakes/cookies, desserts, and sugary drinks (r > .23, P < .04) and lower intake of fruits/berries (r = -.32, P = .044). A higher score in cognitive restraint was associated with a higher intake of cereals and fruits/berries (r > .22, P < .05) and a lower intake of sugary drinks (r = -.24, P< .03).To support optimization of long-term outcomes in adolescent RYGB patients, it is important to provide management strategies to reduce energy intake. Monitoring eating-related problems could identify potential individuals at risk of poor weight loss and to initiate treatment interventions.
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| 10. |
- Järvholm, Kajsa, et al.
(författare)
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5-year mental health and eating pattern outcomes following bariatric surgery in adolescents : a prospective cohort study
- 2020
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Ingår i: The Lancet Child and Adolescent Health. - : Elsevier. - 2352-4642 .- 2352-4650. ; 4:3, s. 210-219
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Tidskriftsartikel (refereegranskat)abstract
- Background: Mental health problems are prevalent among adolescents with severe obesity, but long-term mental health outcomes after adolescent bariatric surgery are not well known. We aimed to assess mental health outcomes over 5 years of follow-up after Roux-en-Y gastric bypass surgery in adolescents who participated in the Adolescent Morbid Obesity Surgery (AMOS) study. Methods: This was a non-randomised matched-control study in adolescents aged 13–18 years who had a BMI of 40 kg/m2 or higher, or 35 kg/m2 or higher in addition to obesity-related comorbidity; who had previously undergone failed comprehensive conservative treatment; and were of pubertal Tanner stage III or higher, with height growth velocity beyond peak. A contemporary control group, matched for BMI, age, and sex, who underwent conventional obesity treatment, was obtained from the Swedish Childhood Obesity Treatment Register. Data on dispensed psychiatric drugs and specialist treatment for mental disorders were retrieved from national registers with complete coverage. In the surgical group only, questionnaires were used to assess self-esteem (Rosenberg Self-Esteem [RSE] score), mood (Mood Adjective Checklist [MACL]), and eating patterns (Binge Eating Scale [BES] and Three-Factor Eating Questionnaire-R21 [TFEQ]). This study is registered with ClinicalTrials.gov (NCT00289705). Findings: Between April 10, 2006, and May 20, 2009, 81 adolescents (53 [65%] female) underwent Roux-en-Y gastric bypass surgery, and 80 control participants received conventional treatment. The proportion of participants prescribed psychiatric drugs did not differ between groups in the years before study inclusion (pre-baseline; absolute risk difference 5% [95% CI −7 to 16], p=0·4263) or after intervention (10% [−6 to 24], p=0·2175). Treatment for mental and behavioural disorders did not differ between groups before baseline (2% [−10 to 14], p=0·7135); however, adolescents in the surgical group had more specialised psychiatric treatment in the 5 years after obesity treatment than did the control group (15% [1 to 28], p=0·0410). There were few patients who discontinued psychiatric treatment post-surgery (three [4%] receiving psychiatric drug treatment and six [7%] receiving specialised care for a mental disorder before surgery). In the surgical group, self-esteem (RSE score) was improved after 5 years (mixed model mean 21·6 [95% CI 19·9 to 23·4]) relative to baseline (18·9 [17·4 to 20·4], p=0·0059), but overall mood (MACL score) was not (2·8 [2·7 to 2·9] at 5 years vs 2·7 [2·6 to 2·8] at baseline, p=0·0737). Binge eating was improved at 5 years (9·3 [7·4 to 11·2]) relative to baseline (15·0 [13·5 to 16·5], p<0·0001). Relative changes in BMI were not associated with the presence or absence of binge eating at baseline. Interpretation: Mental health problems persist in adolescents 5 years after bariatric surgery despite substantial weight loss. Although bariatric surgery can improve many aspects of health, alleviation of mental health problems should not be expected, and a multidisciplinary bariatric team should offer long-term mental health support after surgery. Funding: Swedish Research Council, VINNOVA, Västra Götalandsregionen, ALF VG-region, Region Stockholm, Swedish Child Diabetes Foundation, Swedish Heart and Lung Foundation, Tore Nilsson's Foundation, SUS Foundations and Donations, Capio Research Foundation, and Mary von Sydow's Foundation.
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