SwePub
Sök i SwePub databas

  Utökad sökning

Träfflista för sökning "L773:1061 4036 "

Sökning: L773:1061 4036

Sortera/gruppera träfflistan
   
NumreringReferensOmslagsbildHitta
1.
  • Adrianto, Indra, et al. (författare)
  • Association of a functional variant downstream of TNFAIP3 with systemic lupus erythematosus
  • 2011
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 43:3, s. 253-258
  • Tidskriftsartikel (refereegranskat)abstract
    • Systemic lupus erythematosus (SLE, MIM152700) is an autoimmune disease characterized by self-reactive antibodies resulting in systemic inflammation and organ failure. TNFAIP3, encoding the ubiquitin-modifying enzyme A20, is an established susceptibility locus for SLE. By fine mapping and genomic re-sequencing in ethnically diverse populations, we fully characterized the TNFAIP3 risk haplotype and identified a TT>A polymorphic dinucleotide (deletion T followed by a T to A transversion) associated with SLE in subjects of European (P = 1.58 x 10(-8), odds ratio = 1.70) and Korean (P = 8.33 x 10(-10), odds ratio = 2.54) ancestry. This variant, located in a region of high conservation and regulatory potential, bound a nuclear protein complex composed of NF-kappa B subunits with reduced avidity. Further, compared with the non-risk haplotype, the haplotype carrying this variant resulted in reduced TNFAIP3 mRNA and A20 protein expression. These results establish this TT>A variant as the most likely functional polymorphism responsible for the association between TNFAIP3 and SLE.
  •  
2.
  • Ahmed, Shahana, et al. (författare)
  • Newly discovered breast cancer susceptibility loci on 3p24 and 17q23.2
  • 2009
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 41:5, s. 585-590
  • Tidskriftsartikel (refereegranskat)abstract
    • Genome-wide association studies (GWAS) have identified seven breast cancer susceptibility loci, but these explain only a small fraction of the familial risk of the disease. Five of these loci were identified through a two-stage GWAS involving 390 familial cases and 364 controls in the first stage, and 3,990 cases and 3,916 controls in the second stage. To identify additional loci, we tested over 800 promising associations from this GWAS in a further two stages involving 37,012 cases and 40,069 controls from 33 studies in the CGEMS collaboration and Breast Cancer Association Consortium. We found strong evidence for additional susceptibility loci on 3p (rs4973768: per-allele OR = 1.11, 95% CI = 1.08-1.13, P = 4.1 x 10(-23)) and 17q (rs6504950: per-allele OR = 0.95, 95% CI = 0.92-0.97, P = 1.4 x 10(-8)). Potential causative genes include SLC4A7 and NEK10 on 3p and COX11 on 17q.
  •  
3.
  •  
4.
  • Alvarez, Mariano J., et al. (författare)
  • A precision oncology approach to the pharmacological targeting of mechanistic dependencies in neuroendocrine tumors
  • 2018
  • Ingår i: Nature Genetics. - 1061-4036. ; 50:7, s. 979-989
  • Tidskriftsartikel (refereegranskat)abstract
    • We introduce and validate a new precision oncology framework for the systematic prioritization of drugs targeting mechanistic tumor dependencies in individual patients. Compounds are prioritized on the basis of their ability to invert the concerted activity of master regulator proteins that mechanistically regulate tumor cell state, as assessed from systematic drug perturbation assays. We validated the approach on a cohort of 212 gastroenteropancreatic neuroendocrine tumors (GEP-NETs), a rare malignancy originating in the pancreas and gastrointestinal tract. The analysis identified several master regulator proteins, including key regulators of neuroendocrine lineage progenitor state and immunoevasion, whose role as critical tumor dependencies was experimentally confirmed. Transcriptome analysis of GEP-NET-derived cells, perturbed with a library of 107 compounds, identified the HDAC class I inhibitor entinostat as a potent inhibitor of master regulator activity for 42% of metastatic GEP-NET patients, abrogating tumor growth in vivo. This approach may thus complement current efforts in precision oncology.
  •  
5.
  • Amundadottir, Laufey, et al. (författare)
  • Genome-wide association study identifies variants in the ABO locus associated with susceptibility to pancreatic cancer.
  • 2009
  • Ingår i: Nature Genetics. - 1061-4036. ; 41, s. 986-990
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a two-stage genome-wide association study of pancreatic cancer, a cancer with one of the lowest survival rates worldwide. We genotyped 558,542 SNPs in 1,896 individuals with pancreatic cancer and 1,939 controls drawn from 12 prospective cohorts plus one hospital-based case-control study. We conducted a combined analysis of these groups plus an additional 2,457 affected individuals and 2,654 controls from eight case-control studies, adjusting for study, sex, ancestry and five principal components. We identified an association between a locus on 9q34 and pancreatic cancer marked by the SNP rs505922 (combined P = 5.37 x 10(-8); multiplicative per-allele odds ratio 1.20; 95% confidence interval 1.12-1.28). This SNP maps to the first intron of the ABO blood group gene. Our results are consistent with earlier epidemiologic evidence suggesting that people with blood group O may have a lower risk of pancreatic cancer than those with groups A or B.
  •  
6.
  • Amundadottir, Laufey T., et al. (författare)
  • A common variant associated with prostate cancer in European and African populations
  • 2006
  • Ingår i: Nature Genetics. - 1061-4036. ; 38:6, s. 652-658
  • Tidskriftsartikel (refereegranskat)abstract
    • With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
  •  
7.
  • Anderson, Beverley H., et al. (författare)
  • Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
  • 2012
  • Ingår i: Nature Genetics. - 1061-4036 .- 1546-1718. ; 44:3, s. 338-342
  • Tidskriftsartikel (refereegranskat)abstract
    • Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
  •  
8.
  •  
9.
  •  
10.
  • Arking, Dan E, et al. (författare)
  • Genetic association study of QT interval highlights role for calcium signaling pathways in myocardial repolarization
  • 2014
  • Ingår i: Nature Genetics. - Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 46:8, s. 826-836
  • Tidskriftsartikel (refereegranskat)abstract
    • The QT interval, an electrocardiographic measure reflecting myocardial repolarization, is a heritable trait. QT prolongation is a risk factor for ventricular arrhythmias and sudden cardiac death (SCD) and could indicate the presence of the potentially lethal mendelian long-QT syndrome (LQTS). Using a genome-wide association and replication study in up to 100,000 individuals, we identified 35 common variant loci associated with QT interval that collectively explain ∼8-10% of QT-interval variation and highlight the importance of calcium regulation in myocardial repolarization. Rare variant analysis of 6 new QT interval-associated loci in 298 unrelated probands with LQTS identified coding variants not found in controls but of uncertain causality and therefore requiring validation. Several newly identified loci encode proteins that physically interact with other recognized repolarization proteins. Our integration of common variant association, expression and orthogonal protein-protein interaction screens provides new insights into cardiac electrophysiology and identifies new candidate genes for ventricular arrhythmias, LQTS and SCD.
  •  
Skapa referenser, mejla, bekava och länka
Åtkomst
fritt online (11)
Typ av publikation
tidskriftsartikel (270)
recension (1)
Typ av innehåll
refereegranskat (245)
övrigt vetenskapligt (26)
Författare/redaktör
Uitterlinden, Andre ... (27)
Hayward, Caroline (27)
Metspalu, Andres (27)
Stefansson, Kari (27)
Esko, Tonu (26)
Lind, Lars, (25)
visa fler...
Morris, Andrew P. (24)
Harris, Tamara B. (24)
Gudnason, Vilmundur, (23)
Hofman, Albert, (23)
Rotter, Jerome I., (23)
Gieger, Christian (23)
Wilson, James F. (23)
Rudan, Igor (22)
Loos, Ruth J. F. (22)
Salomaa, Veikko (21)
Van Duijn, Cornelia ... (20)
Langenberg, Claudia (20)
Smith, Albert V., (19)
Deloukas, Panos (19)
Wareham, Nicholas J. (19)
McCarthy, Mark I (19)
Chasman, Daniel I., (19)
Jarvelin, Marjo-Riit ... (19)
Luan, Jian'an (19)
Thorleifsson, Gudmar (19)
Zhao, Jing Hua (19)
Lehtimaki, Terho (19)
Boerwinkle, Eric (19)
Thorsteinsdottir, Un ... (19)
Psaty, Bruce M., (18)
Ridker, Paul M., (18)
Polasek, Ozren (18)
Mahajan, Anubha (18)
Chanock, Stephen J (17)
Boehnke, Michael (17)
Ingelsson, Erik (17)
Hunter, David J. (17)
Perola, Markus (17)
Lindgren, Cecilia M. (17)
Zhang, Weihua (17)
Kooner, Jaspal S. (17)
Khaw, Kay-Tee (16)
Raitakari, Olli T (16)
Launer, Lenore J., (16)
Mohlke, Karen L (16)
Zeggini, Eleftheria (16)
Taylor, Kent D. (16)
Chambers, John C. (16)
Danesh, John (16)
visa färre...
Lärosäte
Karolinska Institutet (148)
Uppsala universitet (128)
Umeå universitet (51)
Lunds universitet (40)
Göteborgs universitet (25)
Örebro universitet (13)
visa fler...
Sveriges Lantbruksuniversitet (9)
Linköpings universitet (8)
Stockholms universitet (8)
Mittuniversitetet (3)
Högskolan Dalarna (3)
Kungliga Tekniska Högskolan (2)
Högskolan i Jönköping (2)
Mälardalens högskola (1)
Chalmers tekniska högskola (1)
visa färre...
Språk
Engelska (271)
Forskningsämne (UKÄ/SCB)
Medicin och hälsovetenskap (162)
Naturvetenskap (50)
Lantbruksvetenskap (8)
Teknik (2)

År

 
pil uppåt Stäng

Kopiera och spara länken för att återkomma till aktuell vy