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Träfflista för sökning "WFRF:(Nilsson Erik D) "

Sökning: WFRF:(Nilsson Erik D)

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1.
  • Dastani, Zari, et al. (författare)
  • Novel loci for adiponectin levels and their influence on type 2 diabetes and metabolic traits : a multi-ethnic meta-analysis of 45,891 individuals.
  • 2012
  • Ingår i: PLoS genetics. - 1553-7404. ; 8:3, s. e1002607
  • Tidskriftsartikel (refereegranskat)abstract
    • Circulating levels of adiponectin, a hormone produced predominantly by adipocytes, are highly heritable and are inversely associated with type 2 diabetes mellitus (T2D) and other metabolic traits. We conducted a meta-analysis of genome-wide association studies in 39,883 individuals of European ancestry to identify genes associated with metabolic disease. We identified 8 novel loci associated with adiponectin levels and confirmed 2 previously reported loci (P = 4.5×10(-8)-1.2×10(-43)). Using a novel method to combine data across ethnicities (N = 4,232 African Americans, N = 1,776 Asians, and N = 29,347 Europeans), we identified two additional novel loci. Expression analyses of 436 human adipocyte samples revealed that mRNA levels of 18 genes at candidate regions were associated with adiponectin concentrations after accounting for multiple testing (p<3×10(-4)). We next developed a multi-SNP genotypic risk score to test the association of adiponectin decreasing risk alleles on metabolic traits and diseases using consortia-level meta-analytic data. This risk score was associated with increased risk of T2D (p = 4.3×10(-3), n = 22,044), increased triglycerides (p = 2.6×10(-14), n = 93,440), increased waist-to-hip ratio (p = 1.8×10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p = 4.4×10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p = 4.5×10(-13), n = 96,748) and decreased BMI (p = 1.4×10(-4), n = 121,335). These findings identify novel genetic determinants of adiponectin levels, which, taken together, influence risk of T2D and markers of insulin resistance.
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2.
  • Palmer, Nicholette D, et al. (författare)
  • A genome-wide association search for type 2 diabetes genes in African Americans.
  • 2012
  • Ingår i: PLoS ONE. - San Francisco : Public Library of Science. - 1932-6203. ; 7:1, s. e29202
  • Tidskriftsartikel (refereegranskat)abstract
    • African Americans are disproportionately affected by type 2 diabetes (T2DM) yet few studies have examined T2DM using genome-wide association approaches in this ethnicity. The aim of this study was to identify genes associated with T2DM in the African American population. We performed a Genome Wide Association Study (GWAS) using the Affymetrix 6.0 array in 965 African-American cases with T2DM and end-stage renal disease (T2DM-ESRD) and 1029 population-based controls. The most significant SNPs (n = 550 independent loci) were genotyped in a replication cohort and 122 SNPs (n = 98 independent loci) were further tested through genotyping three additional validation cohorts followed by meta-analysis in all five cohorts totaling 3,132 cases and 3,317 controls. Twelve SNPs had evidence of association in the GWAS (P<0.0071), were directionally consistent in the Replication cohort and were associated with T2DM in subjects without nephropathy (P<0.05). Meta-analysis in all cases and controls revealed a single SNP reaching genome-wide significance (P<2.5×10(-8)). SNP rs7560163 (P = 7.0×10(-9), OR (95% CI) = 0.75 (0.67-0.84)) is located intergenically between RND3 and RBM43. Four additional loci (rs7542900, rs4659485, rs2722769 and rs7107217) were associated with T2DM (P<0.05) and reached more nominal levels of significance (P<2.5×10(-5)) in the overall analysis and may represent novel loci that contribute to T2DM. We have identified novel T2DM-susceptibility variants in the African-American population. Notably, T2DM risk was associated with the major allele and implies an interesting genetic architecture in this population. These results suggest that multiple loci underlie T2DM susceptibility in the African-American population and that these loci are distinct from those identified in other ethnic populations.
3.
  • Mahajan, Anubha, et al. (författare)
  • Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility
  • 2014
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 46:3, s. 234-
  • Tidskriftsartikel (refereegranskat)abstract
    • To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry.
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4.
  • Nilsson, Sven E., et al. (författare)
  • Långtidsöverlevnaden vid diabetes har successivt förbättrats. Lång sjukdomsduration kan ge information om protektiva möjligheter
  • 2005
  • Ingår i: Läkartidningen. - Sveriges Läkarförbund. - 0023-7205. ; 102:28, s. 2066-2070
  • Tidskriftsartikel (refereegranskat)abstract
    • Studies on patients with long-term diabetes survival without severe complications can give information about protective factors. Therefore, the present study aims to describe the long-term survival of patients with diabetes during successive periods following the introduction of insulin therapy in 1923. After registration in 1973 of the first local diabetic patient in Jonkoping with a fifty-year survival, this group has successively increased. Of those who were diagnosed during the period 1940 through 1949 there was a fifty-year survival in about one third. The successively better survival emphasises the importance of therapeutic progress. The study found no difference in diabetes control between those surviving 50 years and those with an age-matched group with a survival of 15 years. The insulin dose tended to decrease after 30 years duration. Peripheral vibration sensibility as well as renal function deteriorated by longer duration. The serum ratio of HDL-cholesterol to triglycerides increased. The frequency of glaucoma, cataract, and a history of myocardial infarction increased. In spite of long duration, one third of the sample had escaped serious retinopathy.
5.
  • Morris, Andrew P., et al. (författare)
  • Large-scale association analysis provides insights into the genetic architecture and pathophysiology of type 2 diabetes
  • 2012
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 44:9, s. 981-
  • Tidskriftsartikel (refereegranskat)abstract
    • To extend understanding of the genetic architecture and molecular basis of type 2 diabetes (T2D), we conducted a meta-analysis of genetic variants on the Metabochip, including 34,840 cases and 114,981 controls, overwhelmingly of European descent. We identified ten previously unreported T2D susceptibility loci, including two showing sex-differentiated association. Genomewide analyses of these data are consistent with a long tail of additional common variant loci explaining much of the variation in susceptibility to T2D. Exploration of the enlarged set of susceptibility loci implicates several processes, including CREBBP-related transcription, adipocytokine signaling and cell cycle regulation, in diabetes pathogenesis.
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6.
  • Anne, R., et al. (författare)
  • Dissociation Reactions of the Be-11 One-Neutron Halo - the Interplay between Structure and Reaction-Mechanism
  • 1993
  • Ingår i: Physics Letters B. - 0370-2693. ; 304:1-2, s. 55-59
  • Tidskriftsartikel (refereegranskat)abstract
    • The angular distributions of the forward neutrons in the exclusive (Be-10 + n) channel have been measured. They can be accounted for quantitatively and without free parameters in terms of Coulomb and diffraction dissociation. The results show that the transverse momentum distributions result from an interplay between the tail of the wave function (the halo) and the reaction mechanism.
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7.
  • Hogenkamp, Pleunie S, et al. (författare)
  • Acute sleep deprivation increases portion size and affects food choice in young men.
  • 2013
  • Ingår i: Psychoneuroendocrinology. - 1873-3360. ; 38:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Acute sleep loss increases food intake in adults. However, little is known about the influence of acute sleep loss on portion size choice, and whether this depends on both hunger state and the type of food (snack or meal item) offered to an individual. The aim of the current study was to compare portion size choice after a night of sleep and a period of nocturnal wakefulness (a condition experienced by night-shift workers, e.g. physicians and nurses). Sixteen men (age: 23 ± 0.9 years, BMI: 23.6 ± 0.6 kg/m2) participated in a randomized within-subject design with two conditions, 8-h of sleep and total sleep deprivation (TSD). In the morning following sleep interventions, portion size, comprising meal and snack items, was measured using a computer-based task, in both fasted and sated state. In addition, hunger as well as plasma levels of ghrelin were measured. In the morning after TSD, subjects had increased plasma ghrelin levels (13%, p = 0.04), and chose larger portions (14%, p = 0.02), irrespective of the type of food, as compared to the sleep condition. Self-reported hunger was also enhanced (p < 0.01). Following breakfast, sleep-deprived subjects chose larger portions of snacks (16%, p = 0.02), whereas the selection of meal items did not differ between the sleep interventions (6%, p = 0.13). Our results suggest that overeating in the morning after sleep loss is driven by both homeostatic and hedonic factors. Further, they show that portion size choice after sleep loss depend on both an individual's hunger status, and the type of food offered.
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8.
  • Krapohl, David, 1980-, et al. (författare)
  • Investigation of charge collection in a CdTe-Timepix detector
  • 2013
  • Ingår i: Journal of Instrumentation. - 1748-0221. ; 8:May, s. Art. no. C05003
  • Tidskriftsartikel (refereegranskat)abstract
    • Energy calibration of CdTe detectors is usually done using known reference sources disregarding the exact amount of charge that is collected in the pixels. However, to compare detector and detector model the quantity of charge collected is needed. We characterize the charge collection in a CdTe detector comparing test pulses, measured data and an improved TCAD simulation model [1]. The 1 mm thick detector is bump-bonded to a TIMEPIX chip and operating in Time-over-Threshold (ToT) mode. The resistivity in the simulation was adjusted to match the detector properties setting a deep intrinsic donor level [2]. This way it is possible to adjust properties like trap concentration, electron/hole lifetime and mobility in the simulation characterizing the detector close to measured data cite [3].
9.
  • Nilsson, Carol L., et al. (författare)
  • Chromosome 19 Annotations with Disease Speciation: A First Report from the Global Research Consortium
  • 2013
  • Ingår i: Journal of Proteome Research. - 1535-3893. ; 12:1, s. 134-149
  • Tidskriftsartikel (refereegranskat)abstract
    • A first research development progress report of the Chromosome 19 Consortium with members from Sweden, Norway, Spain, United States, China and India, a part of the Chromosome-centric Human Proteome Project (C-HPP) global initiative, is presented (http://www.c-hpp.org). From the chromosome 19 peptide-targeted library constituting 6159 peptides, a pilot study was conducted using a subset with 125 isotope-labeled peptides. We applied an annotation strategy with triple quadrupole, ESI-Qtrap, and MALDI mass spectrometry platforms, comparing the quality of data within and in between these instrumental set-ups. LC-MS conditions were outlined by multiplex assay developments, followed by MRM assay developments. SRM was applied to biobank samples, quantifying kallikrein 3 (prostate specific antigen) in plasma from prostate cancer patients. The antibody production has been initiated for more than 1200 genes from the entire chromosome 19, and the progress developments are presented. We developed a dedicated transcript microarray to serve as the mRNA identifier by screening cancer cell lines. NAPPA protein arrays were built to align with the transcript data with the Chromosome 19 NAPPA chip, dedicated to 90 proteins, as the first development delivery. We have introduced an IT-infrastructure utilizing a LIMS system that serves as the key interface for the research teams to share and explore data generated within the project. The cross-site data repository will form the basis for sample processing, including biological samples as well as patient samples from national Biobanks.
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10.
  • Saxena, Richa, et al. (författare)
  • Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge
  • 2010
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036. ; 42:2, s. 142-U75
  • Tidskriftsartikel (refereegranskat)abstract
    • Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620). We identify variants at the GIPR locus associated with 2- h glucose level (rs10423928, beta (s.e.m.) = 0.09 (0.01) mmol/l per A allele, P = 2.0 x 10(-15)). The GIPR A-allele carriers also showed decreased insulin secretion (n = 22,492; insulinogenic index, P = 1.0 x 10(-17); ratio of insulin to glucose area under the curve, P = 1.3 x 10(-16)) and diminished incretin effect (n = 804; P = 4.3 x 10(-4)). We also identified variants at ADCY5 (rs2877716, P = 4.2 x 10(-16)), VPS13C (rs17271305, P = 4.1 x 10(-8)), GCKR (rs1260326, P = 7.1 x 10(-11)) and TCF7L2 (rs7903146, P = 4.2 x 10(-10)) associated with 2-h glucose. Of the three newly implicated loci (GIPR, ADCY5 and VPS13C), only ADCY5 was found to be associated with type 2 diabetes in collaborating studies (n = 35,869 cases, 89,798 controls, OR = 1.12, 95% CI 1.09-1.15, P = 4.8 x 10(-18)).
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