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- Brolin, Kajsa, et al.
(författare)
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RIC3 variants are not associated with Parkinson's disease in large European, Latin American, or East Asian cohorts
- 2022
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Ingår i: Neurobiology of Aging. - : Elsevier BV. - 0197-4580. ; 109, s. 264-268
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Tidskriftsartikel (refereegranskat)abstract
- Parkinson's disease (PD) is a complex neurodegenerative disorder in which both rare and common genetic variants contribute to disease risk. Multiple genes have been reported to be linked to monogenic PD but these only explain a fraction of the observed familial aggregation. Rare variants in RIC3 have been suggested to be associated with PD in the Indian population. However, replication studies yielded inconsistent results. We further investigate the role of RIC3 variants in PD in European cohorts using individual-level genotyping data from 14,671 PD patients and 17,667 controls, as well as whole-genome sequencing data from 1,615 patients and 961 controls. We also investigated RIC3 using summary statistics from a Latin American cohort of 1,481 individuals, and from a cohort of 31,575 individuals of East Asian ancestry. We did not identify any association between RIC3 and PD in any of the cohorts. However, more studies of rare variants in non-European ancestry populations, in particular South Asian populations, are necessary to further evaluate the world-wide role of RIC3 in PD etiology.
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- Djekic, D., et al.
(författare)
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Effects of a Vegetarian Diet on Cardiometabolic Risk Factors, Gut Microbiota, and Plasma Metabolome in Subjects With Ischemic Heart Disease: A Randomized, Crossover Study
- 2020
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Ingår i: Journal of the American Heart Association. - : Ovid Technologies (Wolters Kluwer Health). - 2047-9980. ; 9:18
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Tidskriftsartikel (refereegranskat)abstract
- Background A vegetarian diet (VD) may reduce future cardiovascular risk in patients with ischemic heart disease. Methods and Results A randomized crossover study was conducted in subjects with ischemic heart disease, assigned to 4-week intervention periods of isocaloric VD and meat diet (MD) with individually designed diet plans, separated by a 4-week washout period. The primary outcome was difference in oxidized low-density lipoprotein cholesterol (LDL-C) between diets. Secondary outcomes were differences in cardiometabolic risk factors, quality of life, gut microbiota, fecal short-chain and branched-chain fatty acids, and plasma metabolome. Of 150 eligible patients, 31 (21%) agreed to participate, and 27 (87%) participants completed the study. Mean oxidized LDL-C (-2.73 U/L), total cholesterol (-5.03 mg/dL), LDL-C (-3.87 mg/dL), and body weight (-0.67 kg) were significantly lower with the VD than with the MD. Differences between VD and MD were observed in the relative abundance of several microbe genera within the families Ruminococcaceae, Lachnospiraceae, and Akkermansiaceae. Plasma metabolites, includingl-carnitine, acylcarnitine metabolites, and phospholipids, differed in subjects consuming VD and MD. The effect on oxidized LDL-C in response to the VD was associated with a baseline gut microbiota composition dominated by several genera of Ruminococcaceae. Conclusions The VD in conjunction with optimal medical therapy reduced levels of oxidized LDL-C, improved cardiometabolic risk factors, and altered the relative abundance of gut microbes and plasma metabolites in patients with ischemic heart disease. Our results suggest that composition of the gut microbiota at baseline may be related to the reduction of oxidized LDL-C observed with the VD.
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- Grenn, Francis P., et al.
(författare)
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The Parkinson's Disease Genome-Wide Association Study Locus Browser
- 2020
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Ingår i: Movement Disorders. - : Wiley. - 0885-3185 .- 1531-8257.
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Tidskriftsartikel (refereegranskat)abstract
- Background: Parkinson's disease (PD) is a neurodegenerative disease with an often complex component identifiable by genome-wide association studies. The most recent large-scale PD genome-wide association studies have identified more than 90 independent risk variants for PD risk and progression across more than 80 genomic regions. One major challenge in current genomics is the identification of the causal gene(s) and variant(s) at each genome-wide association study locus. The objective of the current study was to create a tool that would display data for relevant PD risk loci and provide guidance with the prioritization of causal genes and potential mechanisms at each locus. Methods: We included all significant genome-wide signals from multiple recent PD genome-wide association studies including themost recent PD risk genome-wide association study, age-at-onset genome-wide association study, progression genome-wide association study, and Asian population PD risk genome-wide association study. We gathered data for all genes 1 Mb up and downstream of each variant to allow users to assess which gene(s) are most associated with the variant of interest based on a set of self-ranked criteria. Multiple databases were queried for each gene to collect additional causal data. Results: We created a PD genome-wide association study browser tool (https://pdgenetics.shinyapps.io/GWASBrowser/) to assist the PD research community with the prioritization of genes for follow-up functional studies to identify potential therapeutic targets. Conclusions: Our PD genome-wide association study browser tool provides users with a useful method of identifying potential causal genes at all known PD risk loci from large-scale PD genome-wide association studies. We plan to update this tool with new relevant data as sample sizes increase and new PD risk loci are discovered.
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| 6. |
- Kalin, Kenny, et al.
(författare)
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The effect of saccharin consumption on microbiota composition and insulin sensitivity : a clinical, experimental open label pilot study
- 2020
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Ingår i: Diabetologia. - : Springer. - 0012-186X .- 1432-0428. ; 63:SUPPL 1, s. S223-S224
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background and aims: In a previous study it was suggested that consumption of saccharin, a non-caloric artificial sweetener (NAS), often consumed by individuals with type 2 diabetes mellitus, increases the risk of developing glucose intolerance in rodents and humans through microbiota alterations. However, the study was small and did not use insulin clamp, the gold standard for measuring insulin sensitivity in humans. Thus, our aim was to further investigate whether NAS affect insulin sensitivity and gut microbiota in humans.Materials and methods: We recruited 14 participants (8 women and 6 men) who were non-diabetic, 60.0 (IQR 56.8-64.0) years of age with a body mass index of 27.9 (IQR 27.1-28.5). The study was an open label study where participants acted as their own control. Their insulin sensitivity was measured before and after exposure of 240 mg saccharin/day for three months. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp and the ‘M value’ was calculated by dividing the glucose infusion rate during the last 60 minutes of the clamp by body weight (mg/kg/min). Stool samples were collected before and after saccharin consumption. Microbiota was analyzed by sequencing of the 16S rRNA gene.Results: Thirteen of the 14 participants completed the study. There was no change in insulin resistance after exposure to saccharin (mean M value difference (ΔM) 0.0 (SD 1.6). ΔM was not related to age or sex . Individual M values from the first and second insulin clamp are shown in Figure 1 and indicate some individual responses. During the study 6 participants reduced their HbA1c ≥ 3 mmol/mol. Overall, there was no change in composition or richness of the gut microbiota as a result of saccharin consumption. Furthermore, there was no change in microbiota at end of follow-up for participants with a HbA1c reduction compared to participants without a HbA1c reduction of 3 mmol/mol or more. However, there were small differences in gut microbiota between HbA1c reducers and non-reducers at baseline, with lower gut microbiota diversity in reducers. The reducer group was mainly men who tended to lose more weight than non-reducers; the weight loss was, however, not statistically significant. Statistical analyses of study data were performed by using Student’s t-test.Conclusion: In contrast to prior studies we did not find an effect of NAS on insulin sensitivity. Furthermore, NAS consumption did not alter microbiota composition in these overweight, middle aged adults without type 2 diabetes.
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