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  • Gustafsson, MikaLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden (author)

Integrated genomic and prospective clinical studies show the importance of modular pleiotropy for disease susceptibility, diagnosis and treatment

  • Article/chapterEnglish2014

Publisher, publication year, extent ...

  • BioMed Central,2014
  • electronicrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-106873
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-106873URI
  • https://doi.org/10.1186/gm534DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-97549URI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:128743883URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • Funding agency:Instituto de Salud Carlos III Spanish Government   ISCIII FIS 12/01528, RTICC RD12/0036/0008 
  • Background: Translational research typically aims to identify and functionally validate individual, disease-specific genes. However, reaching this aim is complicated by the involvement of thousands of genes in common diseases, and that many of those genes are pleiotropic, that is, shared by several diseases. Methods: We integrated genomic meta-analyses with prospective clinical studies to systematically investigate the pathogenic, diagnostic and therapeutic roles of pleiotropic genes. In a novel approach, we first used pathway analysis of all published genome-wide association studies (GWAS) to find a cell type common to many diseases. Results: The analysis showed over-representation of the T helper cell differentiation pathway, which is expressed in T cells. This led us to focus on expression profiling of CD4(+) T cells from highly diverse inflammatory and malignant diseases. We found that pleiotropic genes were highly interconnected and formed a pleiotropic module, which was enriched for inflammatory, metabolic and proliferative pathways. The general relevance of this module was supported by highly significant enrichment of genetic variants identified by all GWAS and cancer studies, as well as known diagnostic and therapeutic targets. Prospective clinical studies of multiple sclerosis and allergy showed the importance of both pleiotropic and disease specific modules for clinical stratification. Conclusions: In summary, this translational genomics study identified a pleiotropic module, which has key pathogenic, diagnostic and therapeutic roles.

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  • Edström, MånsLinköpings universitet,Avdelningen för inflammationsmedicin,Hälsouniversitetet,Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping University, Linköping, Sweden(Swepub:oru)msem (author)
  • Gawel, DanutaLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden(Swepub:liu)danga10 (author)
  • Nestor, ColmLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden(Swepub:liu)colne37 (author)
  • Wang, HuiLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden(Swepub:liu)huiwa84 (author)
  • Zhang, HuanLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden(Swepub:liu)huazh47 (author)
  • Barrenäs, FredrikLinköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden(Swepub:liu)freba19 (author)
  • Tojo, JamesDepartment of Clinical Neurosciences, Karolinska Institutet and Centrum for Molecular Medicine, Stockholm, Sweden (author)
  • Kockum, IngridKarolinska Institutet,Karolinska Institute, Sweden Centre Molecular Med, Sweden (author)
  • Olsson, TomasKarolinska Institutet,Karolinska Institute, Sweden Centre Molecular Med, Sweden (author)
  • Serra-Musach, JordiCancer and Systems Biology Unit, Catalan Institute of Oncology, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain (author)
  • Bonifaci, NuriaCancer and Systems Biology Unit, Catalan Institute of Oncology, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain (author)
  • Angel Pujana, MiguelCancer and Systems Biology Unit, Catalan Institute of Oncology, IDIBELL, L'Hospitalet del Llobregat, Barcelona, Spain (author)
  • Ernerudh, JanÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för inflammationsmedicin,Hälsouniversitetet,Klinisk immunologi och transfusionsmedicin,Clinical and Experimental Medicine, Faculty of Health Sciences, Division of Clinical Immunology, Unit of Autoimmunity and Immune Regulation, Linköping University, Linköping, Sweden(Swepub:liu)janer15 (author)
  • Benson, MikaelÖstergötlands Läns Landsting,Linköpings universitet,Avdelningen för kliniska vetenskaper,Hälsouniversitetet,Allergicentrum US,Barn- och ungdomskliniken i Linköping,The Centre for Individualised Medicine, Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden(Swepub:liu)mikbe05 (author)
  • Linköpings universitetAvdelningen för kliniska vetenskaper (creator_code:org_t)

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  • In:Genome Medicine: BioMed Central6:171756-994X

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