SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Lind Lars) srt2:(2015-2019)"

Sökning: WFRF:(Lind Lars) > (2015-2019)

Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
21.
  • Bergström, G, et al. (författare)
  • The Swedish CArdioPulmonary BioImage Study objectives and design
  • 2015
  • Ingår i: Journal of Internal Medicine. - 0954-6820 .- 1365-2796. ; 278:6, s. 645-659
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Cardiopulmonary diseases are major causes of death worldwide, but currently recommended strategies for diagnosis and prevention may be outdated because of recent changes in risk factor patterns. The Swedish CArdioPulmonarybioImage Study (SCAPIS) combines the use of new imaging technologies, advances in large-scale 'omics' and epidemiological analyses to extensively characterize a Swedish cohort of 30 000 men and women aged between 50 and 64 years. The information obtained will be used to improve risk prediction of cardiopulmonary diseases and optimize the ability to study disease mechanisms. A comprehensive pilot study in 1111 individuals, which was completed in 2012, demonstrated the feasibility and financial and ethical consequences of SCAPIS. Recruitment to the national, multicentre study has recently started.</p>
  •  
22.
  •  
23.
  • Dumanski, Jan P., et al. (författare)
  • A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors
  • 2017
  • Ingår i: Endocrine-Related Cancer. - 1351-0088 .- 1479-6821. ; 24:8, s. 427-443
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value = 0.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C- &gt; T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.</p>
  •  
24.
  • Eriksson, Jan W., et al. (författare)
  • Effects of dapagliflozin and n-3 carboxylic acids on non-alcoholic fatty liver disease in people with type 2 diabetes a double-blind randomised placebo-controlled study
  • 2018
  • Ingår i: Diabetologia. - Springer. - 0012-186X .- 1432-0428. ; 61:9, s. 1923-1934
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Aims/hypothesis The EFFECT-II study aimed to investigate the effects of dapagliflozin and omega-3 (n-3) carboxylic acids (OM-3CA). individually or combined, on liver fat content in individuals with type 2 diabetes and non-alcoholic fatty liver disease (NAFLD). Methods This randomised placebo-controlled double-blind parallel-group study was performed at five clinical research centres at university hospitals in Sweden. 84 participants with type 2 diabetes and NAFLD were randomly assigned 1:1:1:1 to four treatments by a centralised randomisation system, and all participants as well as investigators and staff involved in the study conduct and analyses were blinded to treatments. Each group received oral doses of one of the following: 10 mg dapagliflozin (n = 21). 4 g OM3-CA (n = 20), a combination of both (n = 22) or placebo (n = 21). The primary endpoint was liver fat content assessed by MRI (proton density fat fraction [PDFF]) and, in addition, total liver volume and markers of glucose and lipid metabolism as well as of hepatocyte injury and oxidative stress were assessed at baseline and after 12 weeks of treatment (completion of the trial). Results Participants had a mean age of 65.5 years (SD 5.9), BMI 31.2 kg/m(2) (3.5) and liver PDFF 18% (9.3). All active treatments significantly reduced liver PDFF from baseline, relative changes: OM-3CA, -15%; dapagliflozin, -13%; OM-3CA + dapagliflozin, -21%. Only the combination treatment reduced liver PDFF (p = 0.046) and total liver fat volume (relative change, -24%,p = 0.037) in comparison with placebo. There was an interaction between the PNPLA31148M polymorphism and change in liver PDFF in the active treatment groups (p = 0.03). Dapagliflozin monotherapy, but not the combination with OM-3CA, reduced the levels of hepatocyte injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, gamma-glutamyl transfcrase (gamma-GT), cytokeratin (CK) 18-M30 and CK 18-M65 and plasma fibroblast growth factor 21 (FGF21). Changes in gamma-GT correlated with changes in liver PDFF (rho = 0.53, p = 0.02). Dapagliflozin alone and in combination with OM-3CA improved glucose control and reduced body weight and abdominal fat volumes. Fatty acid oxidative stress biomarkers were not affected by treatments. There were no new or unexpected adverse events compared with previous studies with these treatments. Conclusions/interpretation Combined treatment with dapagliflozin and OM-3CA significantly reduced liver fat content. Dapagliflozin monotherapy reduced all measured hepatocyte injury biomarkers and FGF21, suggesting a disease-modifying effect in NAFLD.</p>
  •  
25.
  • Eyjolfsdottir, Helga, et al. (författare)
  • Targeted delivery of nerve growth factor to the cholinergic basal forebrain of Alzheimer's disease patients application of a second-generation encapsulated cell biodelivery device
  • 2016
  • Ingår i: Alzheimer's Research & Therapy. - 1758-9193. ; 8
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>Background: Targeted delivery of nerve growth factor (NGF) has emerged as a potential therapy for Alzheimer's disease (AD) due to its regenerative effects on basal forebrain cholinergic neurons. This hypothesis has been tested in patients with AD using encapsulated cell biodelivery of NGF (NGF-ECB) in a first-in-human study. We report our results from a third-dose cohort of patients receiving second-generation NGF-ECB implants with improved NGF secretion. Methods: Four patients with mild to moderate AD were recruited to participate in an open-label, phase Ib dose escalation study with a 6-month duration. Each patient underwent stereotactic implant surgery with four NGF-ECB implants targeted at the cholinergic basal forebrain. The NGF secretion of the second-generation implants was improved by using the Sleeping Beauty transposon gene expression technology and an improved three-dimensional internal scaffolding, resulting in production of about 10 ng NGF/device/day. Results: All patients underwent successful implant procedures without complications, and all patients completed the study, including implant removal after 6 months. Upon removal, 13 of 16 implants released NGF, 8 implants released NGF at the same rate or higher than before the implant procedure, and 3 implants failed to release detectable amounts of NGF. Of 16 adverse events, none was NGF-, or implant-related. Changes from baseline values of cholinergic markers in cerebrospinal fluid (CSF) correlated with cortical nicotinic receptor expression and Mini Mental State Examination score. Levels of neurofilament light chain (NFL) protein increased in CSF after NGF-ECB implant, while glial fibrillary acidic protein (GFAP) remained stable. Conclusions: The data derived from this patient cohort demonstrate the safety and tolerability of sustained NGF release by a second-generation NGF-ECB implant to the basal forebrain, with uneventful surgical implant and removal of NGF-ECB implants in a new dosing cohort of four patients with AD.</p>
  •  
26.
  • Fall, Tove, et al. (författare)
  • Age- and Sex-Specific Causal Effects of Adiposity on Cardiovascular Risk Factors.
  • 2015
  • Ingår i: Diabetes. - American Diabetes Association Inc.. - 1939-327X. ; 64:5, s. 1841-1852
  • Tidskriftsartikel (refereegranskat)abstract
    • Observational studies have reported different effects of adiposity on cardiovascular risk factors across age and sex. Since cardiovascular risk factors are enriched in obese individuals, it has not been easy to dissect the effects of adiposity from those of other risk factors. We used a Mendelian randomization approach, applying a set of 32 genetic markers to estimate the causal effect of adiposity on blood pressure, glycemic indices, circulating lipid levels, and markers of inflammation and liver disease in up to 67,553 individuals. All analyses were stratified by age (cutoff 55 years of age) and sex. The genetic score was associated with BMI in both nonstratified analysis (P = 2.8 × 10(-107)) and stratified analyses (all P < 3.3 × 10(-30)). We found evidence of a causal effect of adiposity on blood pressure, and fasting levels of insulin, C-reactive protein, interleukin-6, HDL cholesterol, and triglycerides in a nonstratified analysis and in the <55-year stratum. Further, we found evidence of a smaller causal effect on total cholesterol (P for difference = 0.015) in the ≥55-year stratum than in the <55-year stratum, a finding that could be explained by biology, survival bias, or differential medication. In conclusion, this study extends previous knowledge of the effects of adiposity by providing sex- and age-specific causal estimates on cardiovascular risk factors.
  •  
27.
  • Figarska, Sylwia M., et al. (författare)
  • Associations of Circulating Protein Levels With Lipid Fractions in the General Population
  • 2018
  • Ingår i: Arteriosclerosis, Thrombosis, and Vascular Biology. - Lippincott Williams Wilkins Hagerstown, MD. - 1524-4636. ; 38:10, s. 2505-2518
  • Tidskriftsartikel (refereegranskat)abstract
    • Objective- Revealing patterns of associations between circulating protein and lipid levels could improve biological understanding of cardiovascular disease (CVD). In this study, we investigated the associations between proteins related to CVD and triglyceride (TG), total cholesterol, LDL (low-density lipoprotein), and HDL (high-density lipoprotein) cholesterol levels in individuals from the general population. Approach and Results- We measured plasma protein levels using the Olink ProSeek CVD I or II+III arrays and analyzed 57 proteins available in 3 population-based cohorts: EpiHealth (n=2029; 52% women; median age, 61 years), PIVUS (Prospective Study of the Vasculature in Uppsala Seniors; n=790; 51% women; all aged 70 years), and ULSAM (Uppsala Longitudinal Study of Adult Men; n=551; all men aged 77 years). A discovery analysis was performed in EpiHealth in a regression framework (adjusted for sex, age, body mass index, smoking, glucose levels, systolic blood pressure, blood pressure medication, diabetes mellitus medication, and CVD history), and associations with false discovery rate <0.05 were further tested in PIVUS and ULSAM, where a P value of 0.05 was considered a successful replication (validation false discovery rate of 0.1%). We used summary statistics from a genome-wide association study on each protein biomarker (meta-analysis of EpiHealth, PIVUS, ULSAM, and IMPROVE [Carotid Intima-Media Thickness and IMT-Progression as Predictors of Vascular Events in a High-Risk European Population]) and publicly available data from Global Lipids Genetics Consortium to perform Mendelian randomization analyses to address possible causality of protein levels. Of 57 tested proteins, 42 demonstrated an association with at least 1 lipid fraction; 35 were associated with TG, 15 with total cholesterol, 9 with LDL cholesterol, and 24 with HDL cholesterol. Among these associations, we found KIM-1 (kidney injury molecule-1), TNFR (TNF [tumor necrosis factor] receptor) 1 and 2, TRAIL-R2 (TRAIL [TNF-related apoptosis-inducing ligand] receptor 2), and RETN (resistin) to be associated with all 4 lipid fractions. Further, 15 proteins were related to both TG and HDL cholesterol in a consistent and biologically expected manner, that is, higher TG and lower HDL cholesterol or vice versa. Another common pattern of associations was concomitantly higher TG, total cholesterol, and LDL cholesterol, which is associated with higher CVD risk. We did not find evidence of causal links for protein levels. Conclusions- Our comprehensive analysis of plasma proteins and lipid fractions of 3370 individuals from the general population provides new information about lipid metabolism.
  •  
28.
  • Flannick, Jason, et al. (författare)
  • Data Descriptor Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (&gt; 80% of low-frequency coding variants in similar to ~82 K Europeans via the exome chip, and similar to ~90% of low-frequency non-coding variants in similar to ~44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.</p>
  •  
29.
  • Flannick, Jason, et al. (författare)
  • Sequence data and association statistics from 12,940 type 2 diabetes cases and controls
  • 2017
  • Ingår i: Scientific Data. - Nature Publishing Group. - 2052-4463. ; 4
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>To investigate the genetic basis of type 2 diabetes (T2D) to high resolution, the GoT2D and T2D-GENES consortia catalogued variation from whole-genome sequencing of 2,657 European individuals and exome sequencing of 12,940 individuals of multiple ancestries. Over 27M SNPs, indels, and structural variants were identified, including 99% of low-frequency (minor allele frequency [MAF] 0.1-5%) non-coding variants in the whole-genome sequenced individuals and 99.7% of low-frequency coding variants in the whole-exome sequenced individuals. Each variant was tested for association with T2D in the sequenced individuals, and, to increase power, most were tested in larger numbers of individuals (&gt; 80% of low-frequency coding variants in similar to 82 K Europeans via the exome chip, and similar to 90% of low-frequency non-coding variants in similar to 44 K Europeans via genotype imputation). The variants, genotypes, and association statistics from these analyses provide the largest reference to date of human genetic information relevant to T2D, for use in activities such as T2D-focused genotype imputation, functional characterization of variants or genes, and other novel analyses to detect associations between sequence variation and T2D.</p>
  •  
30.
  • Fuchsberger, Christian, et al. (författare)
  • The genetic architecture of type 2 diabetes
  • 2016
  • Ingår i: Nature. - 0028-0836 .- 1476-4687. ; 536:7614, s. 41-47
  • Tidskriftsartikel (refereegranskat)abstract
    • <p>The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes.</p>
  •  
Skapa referenser, mejla, bekava och länka
Åtkomst
fritt online (131)
Typ av publikation
tidskriftsartikel (395)
konferensbidrag (26)
doktorsavhandling (4)
bokkapitel (3)
forskningsöversikt (3)
rapport (1)
visa fler...
visa färre...
Typ av innehåll
refereegranskat (390)
övrigt vetenskapligt (73)
Författare/redaktör
Lind, Lars, (310)
Ingelsson, Erik (110)
Morris, Andrew P. (77)
Mahajan, Anubha (62)
Gustafsson, Stefan (58)
Sundström, Johan, (56)
visa fler...
Salomaa, Veikko (56)
Langenberg, Claudia (55)
Laakso, Markku, (53)
Lindgren, Cecilia M. (53)
Esko, Tonu (50)
Gudnason, Vilmundur (49)
Luan, Jian'an (48)
Giedraitis, Vilmanta ... (47)
Kuusisto, Johanna, (46)
Scott, Robert A (46)
Wareham, Nicholas J (45)
Pedersen, Nancy L (45)
Peters, Annette (45)
Ärnlöv, Johan, (45)
Hayward, Caroline (43)
Boehnke, Michael (42)
Gieger, Christian (42)
Jackson, Anne U. (42)
Zhang, Weihua (42)
Wernersson, Lars-Eri ... (41)
Stancáková, Alena, (41)
Grarup, Niels, (41)
Hansen, Torben, (41)
Collins, Francis S. (41)
Harris, Tamara B. (41)
Metspalu, Andres (41)
Lind, Erik, (41)
Tuomilehto, Jaakko (40)
Melander, Olle, (39)
McCarthy, Mark I (39)
Mohlke, Karen L (39)
Franco, Oscar H (39)
Uitterlinden, Andre ... (38)
Morris, Andrew D (38)
Linneberg, Allan, (37)
Pedersen, Oluf, (37)
Chasman, Daniel I., (37)
Loos, Ruth J. F. (37)
Franks, Paul W, (36)
Teumer, Alexander (36)
Hofman, Albert (36)
Rotter, Jerome I. (36)
Perola, Markus (36)
Stringham, Heather M ... (36)
visa färre...
Lärosäte
Uppsala universitet (184)
Lunds universitet (100)
Umeå universitet (40)
Karolinska Institutet (37)
Högskolan Dalarna (34)
Göteborgs universitet (27)
visa fler...
Linköpings universitet (15)
Örebro universitet (10)
Kungliga Tekniska Högskolan (6)
Stockholms universitet (6)
Chalmers tekniska högskola (5)
Högskolan Kristianstad (3)
Högskolan i Jönköping (3)
Högskolan i Gävle (3)
Södertörns högskola (2)
Ersta Sköndal Bräcke högskola (2)
Högskolan Väst (1)
Mittuniversitetet (1)
Högskolan i Skövde (1)
Linnéuniversitetet (1)
RISE (1)
visa färre...
Språk
Engelska (429)
Svenska (2)
Odefinierat språk (1)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (351)
Teknik (43)
Naturvetenskap (33)
Samhällsvetenskap (9)
Humaniora (2)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy