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Sökning: WFRF:(Egan Sarah J.)

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1.
  • Dupuis, Josee, et al. (författare)
  • New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk
  • 2010
  • Ingår i: Nature Genetics. - : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 42:2, s. 32-105
  • Tidskriftsartikel (refereegranskat)abstract
    • Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes.
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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 .- 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.
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3.
  • Manning, Alisa K., et al. (författare)
  • A genome-wide approach accounting for body mass index identifies genetic variants influencing fasting glycemic traits and insulin resistance
  • 2012
  • Ingår i: Nature Genetics. - New York : Nature Publishing Group. - 1546-1718 .- 1061-4036. ; 44:6, s. 81-659
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent genome-wide association studies have described many loci implicated in type 2 diabetes (T2D) pathophysiology and beta-cell dysfunction but have contributed little to the understanding of the genetic basis of insulin resistance. We hypothesized that genes implicated in insulin resistance pathways might be uncovered by accounting for differences in body mass index (BMI) and potential interactions between BMI and genetic variants. We applied a joint meta-analysis approach to test associations with fasting insulin and glucose on a genome-wide scale. We present six previously unknown loci associated with fasting insulin at P < 5 x 10(-8) in combined discovery and follow-up analyses of 52 studies comprising up to 96,496 non-diabetic individuals. Risk variants were associated with higher triglyceride and lower high-density lipoprotein (HDL) cholesterol levels, suggesting a role for these loci in insulin resistance pathways. The discovery of these loci will aid further characterization of the role of insulin resistance in T2D pathophysiology.
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4.
  • Natali, S. M., et al. (författare)
  • Large loss of CO2 in winter observed across the northern permafrost region
  • 2019
  • Ingår i: Nature Climate Change. - : Nature Research. - 1758-678X .- 1758-6798. ; 9:11, s. 852-857
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent warming in the Arctic, which has been amplified during the winter(1-3), greatly enhances microbial decomposition of soil organic matter and subsequent release of carbon dioxide (CO2)(4). However, the amount of CO2 released in winter is not known and has not been well represented by ecosystem models or empirically based estimates(5,6). Here we synthesize regional in situ observations of CO2 flux from Arctic and boreal soils to assess current and future winter carbon losses from the northern permafrost domain. We estimate a contemporary loss of 1,662 TgC per year from the permafrost region during the winter season (October-April). This loss is greater than the average growing season carbon uptake for this region estimated from process models (-1,032 TgC per year). Extending model predictions to warmer conditions up to 2100 indicates that winter CO2 emissions will increase 17% under a moderate mitigation scenario-Representative Concentration Pathway 4.5-and 41% under business-as-usual emissions scenario-Representative Concentration Pathway 8.5. Our results provide a baseline for winter CO2 emissions from northern terrestrial regions and indicate that enhanced soil CO2 loss due to winter warming may offset growing season carbon uptake under future climatic conditions.
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5.
  • 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. - 1553-7390 .- 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 x 10(-8)-1.2 x 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 x 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 x 10(-3), n = 22,044), increased triglycerides (p=2.6 x 10(-14), n = 93,440), increased waist-to-hip ratio (p=1.8 x 10(-5), n = 77,167), increased glucose two hours post oral glucose tolerance testing (p=4.4 x 10(-3), n = 15,234), increased fasting insulin (p = 0.015, n = 48,238), but with lower in HDL-cholesterol concentrations (p=4.5x10(-13), n = 96,748) and decreased BMI (p= 1.4 x 10(-14), 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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6.
  • Johnson, Shevaugn, et al. (författare)
  • Internet-delivered cognitive behavioural therapy for perfectionism : Targeting dysmorphic concern
  • 2019
  • Ingår i: Body image. - : Elsevier. - 1740-1445 .- 1873-6807. ; 30, s. 44-55
  • Tidskriftsartikel (refereegranskat)abstract
    • Perfectionism is an important transdiagnostic risk factor for several psychopathologies. As such, treatments targeting perfectionism have gained increased attention over recent years. While perfectionism is postulated to be an important underlying mechanism for dysmorphic concern, no research has explored the benefits of targeting perfectionism to reduce dysmorphic concern. The current study evaluated the use of Internet-delivered cognitive behavioural therapy for perfectionism (ICBT-P) with 31 participants (28 women) with high levels of dysmorphic concern to examine the impact on perfectionism, dysmorphic concern, body image disturbance, negative affect, and selective attention towards appearance-based stimuli. Using a case series design, observations were collected at baseline, at the end of a 4-week pre-treatment phase, after the 8-week ICBT-P, and 1-month post-treatment. Intent-to-treat analyses showed significant improvement from baseline to end-of-treatment and follow-up on most of the variables, with a large effect size decrease in dysmorphic concern, and decreased selective attention to BDD-body, BDD-positive, and BDD-negative words. The results of this study support the use of ICBT-P as an efficacious treatment worthy of further examination in populations who experience high levels of dysmorphic concern.
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7.
  • Rozental, Alexander, et al. (författare)
  • Guided web-based cognitive behavior therapy for perfectionism : Results from two different randomized controlled trials
  • 2018
  • Ingår i: Journal of Medical Internet Research. - : JMIR PUBLICATIONS, INC. - 1438-8871 .- 1438-8871. ; 20:4
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Perfectionism can become a debilitating condition that may negatively affect functioning in multiple areas, including mental health. Prior research has indicated that internet-based cognitive behavioral therapy can be beneficial, but few studies have included follow-up data.Objective: The objective of this study was to explore the outcomes at follow-up of internet-based cognitive behavioral therapy with guided self-help, delivered as 2 separate randomized controlled trials conducted in Sweden and the United Kingdom.Methods: In total, 120 participants randomly assigned to internet-based cognitive behavioral therapy were included in both intention-to-treat and completer analyses: 78 in the Swedish trial and 62 in the UK trial. The primary outcome measure was the Frost Multidimensional Perfectionism Scale, Concern over Mistakes subscale (FMPS CM). Secondary outcome measures varied between the trials and consisted of the Clinical Perfectionism Questionnaire (CPQ; both trials), the 9-item Patient Health Questionnaire (PHQ-9; Swedish trial), the 7-item Generalized Anxiety Disorder scale (GAD-7; Swedish trial), and the 21-item Depression Anxiety Stress Scale (DASS-21; UK trial). Follow-up occurred after 6 months for the UK trial and after 12 months for the Swedish trial.Results: Analysis of covariance revealed a significant difference between pretreatment and follow-up in both studies. Intention-to-treat within-group Cohen d effect sizes were 1.21 (Swedish trial; 95% CI 0.86-1.54) and 1.24 (UK trial; 95% CI 0.85-1.62) for the FMPS CM. Furthermore, 29 (59%; Swedish trial) and 15 (43%; UK trial) of the participants met the criteria for recovery on the FMPS CM. Improvements were also significant for the CPQ, with effect sizes of 1.32 (Swedish trial; 95% CI 0.97-1.66) and 1.49 (UK trial; 95% CI 1.09-1.88); the PHQ-9, effect size 0.60 (95% CI 0.28-0.92); the GAD-7, effect size 0.67 (95% CI 0.34-0.99); and the DASS-21, effect size 0.50 (95% CI 0.13-0.85).Conclusions: The results are promising for the use of internet-based cognitive behavioral therapy as a way of targeting perfectionism, but the findings need to be replicated and include a comparison condition.
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8.
  • Shafran, Roz, et al. (författare)
  • Is the devil in the detail? A randomised controlled trial of guided internet-based CBT for perfectionism
  • 2017
  • Ingår i: Behaviour Research and Therapy. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0005-7967 .- 1873-622X. ; 95, s. 99-106
  • Tidskriftsartikel (refereegranskat)abstract
    • An Internet guided self-help cognitive-behavioural treatment (ICBT) for perfectionism was recently found to be effective (see this issue). Such studies stand in need of replication. The aim of this study was to report the outcomes and predictors of change when the treatment is delivered in a UK setting. A total of 120 people (Mean = 28.9 years; 79% female) were randomised to receive ICBT or wait-list control over 12 weeks (trial registration: NCT02756871). While there were strong similarities between the current study and its Swedish counterpart, there were also important differences in procedural details. There was a significant impact of the intervention on the primary outcome measure (Frost Multidimensional Perfectionism Scale, Concern over Mistakes subscale) and also on the Clinical Perfectionism Questionnaire (between group effect sizes d = 0.98 (95% CI: 0.60-1.36) and d = 1.04 (95% CI: 0.66-1.43) respectively using intent-to-treat analyses). Unlike the Swedish study, there was significant non engagement and non-completion of modules with 71% of participants completing fewer than half the modules. The number of modules completed moderated the rate of change in clinical perfectionism over time. In conclusion, the study indicates the intervention is effective in a UK setting but highlighted the importance of procedural details to optimise retention. (C) 2017 Elsevier Ltd. All rights reserved.
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9.
  • Wade, Tracey D., et al. (författare)
  • Internet-based cognitive behaviour therapy for perfectionism : More is better but no need to be prescriptive
  • 2019
  • Ingår i: Clinical Psychologist. - : Wiley-Blackwell Publishing Inc.. - 1328-4207 .- 1742-9552. ; 23:3, s. 196-205
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: The current study explored whether higher- (up to 8 modules) versus lower-dose (3 or less modules) unguided internet Cognitive Behaviour Therapy for perfectionism (ICBT-P) was more effective, and the best method to promote higher dosage.Methods: Two sequential randomised ICBT-P studies were conducted with participants who self-identified as having difficulties with perfectionism; in the first participants (N = 51) received 3-module ICBT-P or wait-list, and in the second participants (N = 55) received fixed (asked to complete all 8 modules two per week over 4-weeks) or flexible format (after completing the first psychoeducational module, participants decided how many/in what order they completed the modules). We examined impact on our primary variables, perfectionistic concerns and standards, and secondary outcomes of negative affect, body image flexibility, and self-efficacy.Results: More modules were completed in the higher- (M modules = 4.36, SD = 3.29) versus lower-dose (M = 1.96, SD = 1.23) ICBT-P, d = 0.86 (95% confidence interval: 0.39, 1.34). The latter impacted perfectionism but not secondary outcomes; the former impacted all outcomes (except for self-efficacy), and within-group effect size improvements were double in the high- compared to low-dose ICBT-P. There was no difference between the fixed and flexible formats in terms of the number of modules completed or impact.Conclusions: We can offer a patient-centred approach to ICBT-P that is effective, while suggesting completion of more modules can result in larger, more pervasive improvements.ANZCTR Trial Number: ACTRN12619000147189.
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10.
  • Shafran, Roz (författare)
  • Is the devil in the detail? : A randomised controlled trial of guided internet-based CBT for perfectionism
  • 2017
  • Ingår i: Behaviour Research and Therapy. - 0005-7967 .- 1873-622X. ; 95, s. 99-106
  • Tidskriftsartikel (refereegranskat)abstract
    • An internet guided self-help cognitive-behavioural treatment (ICBT) for perfectionism was recently found to be effective (see this issue). Such studies stand in need of replication. The aim of this study was to report the outcomes and predictors of change when the treatment is delivered in a UK setting. A total of 120 people (Mean = 28.9 years; 79% female) were randomised to receive ICBT or wait-list control over 12 weeks (trial registration: NCT02756871). While there were strong similarities between the current study and its Swedish counterpart, there were also important differences in procedural details. There was a significant impact of the intervention on the primary outcome measure (Frost Multidimensional Perfectionism Scale, Concern over Mistakes subscale) and also on the Clinical Perfectionism Questionnaire (between group effect sizes d = 0.98 (95% CI: 0.60–1.36) and d = 1.04 (95% CI: 0.66–1.43) respectively using intent-to-treat analyses). Unlike the Swedish study, there was significant non-engagement and non-completion of modules with 71% of participants completing fewer than half the modules. The number of modules completed moderated the rate of change in clinical perfectionism over time. In conclusion, the study indicates the intervention is effective in a UK setting but highlighted the importance of procedural details to optimise retention.
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