SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "WFRF:(Goyette Philippe) "

Sökning: WFRF:(Goyette Philippe)

  • Resultat 1-10 av 11
  • [1]2Nästa
Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • den Hoed, Marcel, et al. (författare)
  • Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders
  • 2013
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 45:6, s. 621-
  • Tidskriftsartikel (refereegranskat)abstract
    • Elevated resting heart rate is associated with greater risk of cardiovascular disease and mortality. In a 2-stage meta-analysis of genome-wide association studies in up to 181,171 individuals, we identified 14 new loci associated with heart rate and confirmed associations with all 7 previously established loci. Experimental downregulation of gene expression in Drosophila melanogaster and Danio rerio identified 20 genes at 11 loci that are relevant for heart rate regulation and highlight a role for genes involved in signal transmission, embryonic cardiac development and the pathophysiology of dilated cardiomyopathy, congenital heart failure and/or sudden cardiac death. In addition, genetic susceptibility to increased heart rate is associated with altered cardiac conduction and reduced risk of sick sinus syndrome, and both heart rate-increasing and heart rate-decreasing variants associate with risk of atrial fibrillation. Our findings provide fresh insights into the mechanisms regulating heart rate and identify new therapeutic targets.
  •  
2.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1546-1718. ; 42:11, s. 53-937
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and similar to 2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 x 10(-8)), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
  •  
3.
  • Ashar, Foram N, et al. (författare)
  • A comprehensive evaluation of the genetic architecture of sudden cardiac arrest
  • 2018
  • Ingår i: European Heart Journal. - Oxford University Press. - 0195-668X. ; 39:44, s. 3961-
  • Tidskriftsartikel (refereegranskat)abstract
    • Aims: Sudden cardiac arrest (SCA) accounts for 10% of adult mortality in Western populations. We aim to identify potential loci associated with SCA and to identify risk factors causally associated with SCA.Methods and results: We carried out a large genome-wide association study (GWAS) for SCA (n = 3939 cases, 25 989 non-cases) to examine common variation genome-wide and in candidate arrhythmia genes. We also exploited Mendelian randomization (MR) methods using cross-trait multi-variant genetic risk score associations (GRSA) to assess causal relationships of 18 risk factors with SCA. No variants were associated with SCA at genome-wide significance, nor were common variants in candidate arrhythmia genes associated with SCA at nominal significance. Using cross-trait GRSA, we established genetic correlation between SCA and (i) coronary artery disease (CAD) and traditional CAD risk factors (blood pressure, lipids, and diabetes), (ii) height and BMI, and (iii) electrical instability traits (QT and atrial fibrillation), suggesting aetiologic roles for these traits in SCA risk.Conclusions: Our findings show that a comprehensive approach to the genetic architecture of SCA can shed light on the determinants of a complex life-threatening condition with multiple influencing factors in the general population. The results of this genetic analysis, both positive and negative findings, have implications for evaluating the genetic architecture of patients with a family history of SCA, and for efforts to prevent SCA in high-risk populations and the general community.
  •  
4.
  • Beaudoin, Melissa, et al. (författare)
  • Deep Resequencing of GWAS Loci Identifies Rare Variants in CARD9, IL23R and RNF186 That Are Associated with Ulcerative Colitis
  • 2013
  • Ingår i: PLOS Genetics. - Public Library of Science (PLoS). - 1553-7390. ; 9:9
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies and follow-up meta-analyses in Crohn's disease (CD) and ulcerative colitis (UC) have recently identified 163 disease-associated loci that meet genome-wide significance for these two inflammatory bowel diseases (IBD). These discoveries have already had a tremendous impact on our understanding of the genetic architecture of these diseases and have directed functional studies that have revealed some of the biological functions that are important to IBD (e.g. autophagy). Nonetheless, these loci can only explain a small proportion of disease variance (similar to 14% in CD and 7.5% in UC), suggesting that not only are additional loci to be found but that the known loci may contain high effect rare risk variants that have gone undetected by GWAS. To test this, we have used a targeted sequencing approach in 200 UC cases and 150 healthy controls (HC), all of French Canadian descent, to study 55 genes in regions associated with UC. We performed follow-up genotyping of 42 rare non-synonymous variants in independent case-control cohorts (totaling 14,435 UC cases and 20,204 HC). Our results confirmed significant association to rare non-synonymous coding variants in both IL23R and CARD9, previously identified from sequencing of CD loci, as well as identified a novel association in RNF186. With the exception of CARD9 (OR = 0.39), the rare non-synonymous variants identified were of moderate effect (OR = 1.49 for RNF186 and OR = 0.79 for IL23R). RNF186 encodes a protein with a RING domain having predicted E3 ubiquitin-protein ligase activity and two transmembrane domains. Importantly, the disease-coding variant is located in the ubiquitin ligase domain. Finally, our results suggest that rare variants in genes identified by genome-wide association in UC are unlikely to contribute significantly to the overall variance for the disease. Rather, these are expected to help focus functional studies of the corresponding disease loci.
5.
  • Cleynen, Isabelle, et al. (författare)
  • Inherited determinants of Crohn's disease and ulcerative colitis phenotypes a genetic association study
  • 2016
  • Ingår i: The Lancet. - New York, USA : Elsevier. - 0140-6736. ; 387:10014, s. 156-167
  • Tidskriftsartikel (refereegranskat)abstract
    • Background: Crohn's disease and ulcerative colitis are the two major forms of inflammatory bowel disease; treatment strategies have historically been determined by this binary categorisation. Genetic studies have identified 163 susceptibility loci for inflammatory bowel disease, mostly shared between Crohn's disease and ulcerative colitis. We undertook the largest genotype association study, to date, in widely used clinical subphenotypes of inflammatory bowel disease with the goal of further understanding the biological relations between diseases.Methods This study included patients from 49 centres in 16 countries in Europe, North America, and Australasia. We applied the Montreal classification system of inflammatory bowel disease subphenotypes to 34,819 patients (19,713 with Crohn's disease, 14,683 with ulcerative colitis) genotyped on the Immunochip array. We tested for genotype-phenotype associations across 156,154 genetic variants. We generated genetic risk scores by combining information from all known inflammatory bowel disease associations to summarise the total load of genetic risk for a particular phenotype. We used these risk scores to test the hypothesis that colonic Crohn's disease, ileal Crohn's disease, and ulcerative colitis are all genetically distinct from each other, and to attempt to identify patients with a mismatch between clinical diagnosis and genetic risk profile.Findings: After quality control, the primary analysis included 29,838 patients (16,902 with Crohn's disease, 12,597 with ulcerative colitis). Three loci (NOD2, MHC, and MST1 3p21) were associated with subphenotypes of inflammatory bowel disease, mainly disease location (essentially fixed over time; median follow-up of 10·5 years). Little or no genetic association with disease behaviour (which changed dramatically over time) remained after conditioning on disease location and age at onset. The genetic risk score representing all known risk alleles for inflammatory bowel disease showed strong association with disease subphenotype (p=1·65 × 10(-78)), even after exclusion of NOD2, MHC, and 3p21 (p=9·23 × 10(-18)). Predictive models based on the genetic risk score strongly distinguished colonic from ileal Crohn's disease. Our genetic risk score could also identify a small number of patients with discrepant genetic risk profiles who were significantly more likely to have a revised diagnosis after follow-up (p=6·8 × 10(-4)).Interpretation: Our data support a continuum of disorders within inflammatory bowel disease, much better explained by three groups (ileal Crohn's disease, colonic Crohn's disease, and ulcerative colitis) than by Crohn's disease and ulcerative colitis as currently defined. Disease location is an intrinsic aspect of a patient's disease, in part genetically determined, and the major driver to changes in disease behaviour over time.Funding: International Inflammatory Bowel Disease Genetics Consortium members funding sources (see Acknowledgments for full list).
6.
  • Goyette, Philippe, et al. (författare)
  • High-density mapping of the MHC identifies a shared role for HLA-DRB1*01 : 03 in inflammatory bowel diseases and heterozygous advantage in ulcerative colitis
  • 2015
  • Ingår i: Nature Genetics. - New York, USA : Nature Publishing Group. - 1061-4036. ; 47:2, s. 172-179
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies of the related chronic inflammatory bowel diseases (IBD) known as Crohn's disease and ulcerative colitis have shown strong evidence of association to the major histocompatibility complex (MHC). This region encodes a large number of immunological candidates, including the antigen-presenting classical human leukocyte antigen (HLA) molecules. Studies in IBD have indicated that multiple independent associations exist at HLA and non-HLA genes, but they have lacked the statistical power to define the architecture of association and causal alleles. To address this, we performed high-density SNP typing of the MHC in &gt;32,000 individuals with IBD, implicating multiple HLA alleles, with a primary role for HLA-DRB1*01:03 in both Crohn's disease and ulcerative colitis. Noteworthy differences were observed between these diseases, including a predominant role for class II HLA variants and heterozygous advantage observed in ulcerative colitis, suggesting an important role of the adaptive immune response in the colonic environment in the pathogenesis of IBD.
  •  
7.
  • McCarroll, Steven A, et al. (författare)
  • Deletion polymorphism upstream of IRGM associated with altered IRGM expression and Crohn's disease
  • 2008
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 40:9, s. 1107-1112
  • Tidskriftsartikel (refereegranskat)abstract
    • Following recent success in genome-wide association studies, a critical focus of human genetics is to understand how genetic variation at implicated loci influences cellular and disease processes. Crohn's disease (CD) is associated with SNPs around IRGM, but coding-sequence variation has been excluded as a source of this association. We identified a common, 20-kb deletion polymorphism, immediately upstream of IRGM and in perfect linkage disequilibrium (r2 = 1.0) with the most strongly CD-associated SNP, that causes IRGM to segregate in the population with two distinct upstream sequences. The deletion (CD risk) and reference (CD protective) haplotypes of IRGM showed distinct expression patterns. Manipulation of IRGM expression levels modulated cellular autophagy of internalized bacteria, a process implicated in CD. These results suggest that the CD association at IRGM arises from an alteration in IRGM regulation that affects the efficacy of autophagy and identify a common deletion polymorphism as a likely causal variant.
  •  
8.
  • McGovern, Dermot P. B., et al. (författare)
  • Genome-wide association identifies multiple ulcerative colitis susceptibility loci
  • 2010
  • Ingår i: Nature Genetics. - 1061-4036. ; 42:4, s. 332-337
  • Tidskriftsartikel (refereegranskat)abstract
    • Ulcerative colitis is a chronic, relapsing inflammatory condition of the gastrointestinal tract with a complex genetic and environmental etiology. In an effort to identify genetic variation underlying ulcerative colitis risk, we present two distinct genome-wide association studies of ulcerative colitis and their joint analysis with a previously published scan, comprising, in aggregate, 2,693 individuals with ulcerative colitis and 6,791 control subjects. Fifty-nine SNPs from 14 independent loci attained an association significance of P &lt; 10(-5). Seven of these loci exceeded genome-wide significance (P &lt; 5 x 10(-8)). After testing an independent cohort of 2,009 cases of ulcerative colitis and 1,580 controls, we identified 13 loci that were significantly associated with ulcerative colitis (P &lt; 5 x 10(-8)), including the immunoglobulin receptor gene FCGR2A, 5p15, 2p16 and ORMDL3 (orosomucoid1-like 3). We confirmed association with 14 previously identified ulcerative colitis susceptibility loci, and an analysis of acknowledged Crohn's disease loci showed that roughly half of the known Crohn's disease associations are shared with ulcerative colitis. These data implicate approximately 30 loci in ulcerative colitis, thereby providing insight into disease pathogenesis.
  •  
9.
  •  
10.
  • Rivas, Manuel A., et al. (författare)
  • A protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
  • 2016
  • Ingår i: Nature Communications. - London, United Kingdom : Nature Publishing Group. - 2041-1723. ; 7
  • Tidskriftsartikel (refereegranskat)abstract
    • Protein-truncating variants protective against human disease provide in vivo validation of therapeutic targets. Here we used targeted sequencing to conduct a search for protein-truncating variants conferring protection against inflammatory bowel disease exploiting knowledge of common variants associated with the same disease. Through replication genotyping and imputation we found that a predicted protein-truncating variant (rs36095412, p.R179X, genotyped in 11,148 ulcerative colitis patients and 295,446 controls, MAF=up to 0.78%) in RNF186, a single-exon ring finger E3 ligase with strong colonic expression, protects against ulcerative colitis (overall P=6.89 × 10(-7), odds ratio=0.30). We further demonstrate that the truncated protein exhibits reduced expression and altered subcellular localization, suggesting the protective mechanism may reside in the loss of an interaction or function via mislocalization and/or loss of an essential transmembrane domain.
Skapa referenser, mejla, bekava och länka
  • Resultat 1-10 av 11
  • [1]2Nästa
Åtkomst
fritt online (3)
Typ av publikation
tidskriftsartikel (11)
Typ av innehåll
refereegranskat (11)
Författare/redaktör
Silverberg, Mark S (7)
Franke, Andre (5)
Weersma, Rinse K (5)
Rotter, Jerome I., (4)
Halfvarson, Jonas, 1 ... (3)
Hofman, Albert, (3)
visa fler...
Salomaa, Veikko (3)
Havulinna, Aki S. (3)
Lettre, Guillaume (3)
Glazer, Nicole L. (3)
Khaw, Kay-Tee (2)
Froguel, Philippe, (2)
Viikari, Jorma (2)
Chanock, Stephen J (2)
Soranzo, Nicole (2)
Boomsma, Dorret I., (2)
Gudnason, Vilmundur, (2)
Hottenga, Jouke-Jan, (2)
Montgomery, Grant W. ... (2)
Psaty, Bruce M., (2)
Uitterlinden, Andre ... (2)
Martin, Nicholas G., (2)
Wareham, Nicholas J. (2)
Almgren, Peter, (2)
Isomaa, Bo, (2)
Hu, Frank B., (2)
Qi, Lu (2)
Ahmad, Tariq, (2)
Kraft, Peter (2)
Ellinghaus, David (2)
Schreiber, Stefan (2)
Willemsen, Gonneke (2)
Peters, Annette (2)
Samani, Nilesh J. (2)
Jarvelin, Marjo-Riit ... (2)
Padyukov, Leonid, (2)
Lorentzon, Mattias, (2)
Weedon, Michael N. (2)
Jackson, Anne U. (2)
Segre, Ayellet V. (2)
Yang, Jian (2)
Gudbjartsson, Daniel (2)
Luan, Jian'an (2)
Lo, Ken Sin (2)
Feitosa, Mary F. (2)
Esko, Tonu (2)
Johnson, Toby (2)
Ketkar, Shamika (2)
Hayward, Caroline (2)
Knowles, Joshua W. (2)
visa färre...
Lärosäte
Karolinska Institutet (9)
Örebro universitet (7)
Uppsala universitet (4)
Lunds universitet (3)
Göteborgs universitet (2)
Umeå universitet (1)
Språk
Engelska (11)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (10)
Naturvetenskap (2)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy