Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms

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Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms

Barrenäs, Fredrik (författare): Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Universitetssjukhuset i Linköping,Linköping University Hospital

Chavali, Sreenivas (författare): MRC-Laboratory of Molecular Biology, University of Cambridge, Hills Road, Cambridge, CB2 0QH, UK,University Of Cambridge

Alves, Alexessander Couto (författare): Department of Genomics of Common Disease, School of Public Health, Imperial College, UK,Imperial College of Science, Technology and Medicine

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Coin, Lachlan (författare): Department of Genomics of Common Disease, School of Public Health, Imperial College, UK,Imperial College of Science, Technology and Medicine

Jarvelin, Marjo-Riitta (författare): Department of Genomics of Common Disease, School of Public Health, Imperial College, UK,Oulun Yliopisto,University of Oulu,Imperial College of Science, Technology and Medicine

Jörnsten, Rebecka, 1971 (författare): Gothenburg University,Göteborgs universitet,Institutionen för matematiska vetenskaper, matematisk statistik,Department of Mathematical Sciences, Mathematical Statistics,Mathematical Sciences, Chalmers University of Technology, University of Gothenburg, Gothenburg, Sweden

Langston, Michael A (författare): Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, USA,University of Tennessee

Ramasamy, Adaikalavan (författare): Department of Genomics of Common Disease, School of Public Health, Imperial College, London, UK,Imperial College of Science, Technology and Medicine

Rogers, Gary (författare): Department of Electrical Engineering and Computer Science, University of Tennessee, Knoxville, USA,University of Tennessee

Wang, Hui (författare): Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Universitetssjukhuset i Linköping,Linköping University Hospital

Benson, Mikael (författare): Linköpings universitet,Institutionen för klinisk och experimentell medicin,Hälsouniversitetet,Universitetssjukhuset i Linköping,Linköping University Hospital,Sahlgrenska universitetssjukhuset,Sahlgrenska University Hospital

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(creator_code:org_t)

BioMed Central, 2012
2012
Engelska.
Ingår i: Genome Biology. - : BioMed Central. - 1465-6906 .- 1474-760X .- 1465-6914. ; 13:6, s. R46-

Relaterad länk:: https://liu.diva-por... (primary) (Raw object); visa fler...; https://genomebiolog...; http://publications.... (primary) (free); https://gup.ub.gu.se... (primary) (free); https://urn.kb.se/re...; https://doi.org/10.1...; https://research.cha...; https://gup.ub.gu.se...; visa färre...

Tidskriftsartikel (refereegranskat)

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BACKGROUND: Complex diseases are associated with altered interactions between thousands of genes. We developed a novel method to identify and prioritize disease genes, which was generally applicable to complex diseases.RESULTS: We identified modules of highly interconnected genes in disease-specific networks derived from integrating gene-expression and protein interaction data. We examined if those modules were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies. First, we analyzed publicly available gene expression microarray and genome-wide association study (GWAS) data from 13, highly diverse, complex diseases. In each disease, highly interconnected genes formed modules, which were significantly enriched for genes harboring disease-associated SNPs. To test if such modules could be used to find novel genes for functional studies, we repeated the analyses using our own gene expression microarray and GWAS data from seasonal allergic rhinitis. We identified a novel gene, FGF2, whose relevance was supported by functional studies using combined small interfering RNA-mediated knock-down and gene expression microarrays. The modules in the 13 complex diseases analyzed here tended to overlap and were enriched for pathways related to oncological, metabolic and inflammatory diseases. This suggested that this union of the modules would be associated with a general increase in susceptibility for complex diseases. Indeed, we found that this union was enriched with GWAS genes for 145 other complex diseases.CONCLUSIONS: Modules of highly interconnected complex disease genes were enriched for disease-associated SNPs, and could be used to find novel genes for functional studies.

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Av författaren/redakt...: Barrenäs, Fredri ...; Chavali, Sreeniv ...; Alves, Alexessan ...; Coin, Lachlan; Jarvelin, Marjo- ...; Jörnsten, Rebeck ...; visa fler...; Langston, Michae ...; Ramasamy, Adaika ...; Rogers, Gary; Wang, Hui; Benson, Mikael; visa färre...

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MEDICIN OCH HÄLSOVETENSKAP: MEDICIN OCH HÄLS ...; och Klinisk medicin; och Pediatrik

Artiklar i publikationen: Genome Biology

Av lärosätet: Linköpings universitet; Chalmers tekniska högskola; Göteborgs universitet

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Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms

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