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

Barrenas, Fredrik, Chavali, Sreenivas, Couto Alves, Alexessander, Coin, Lachlan, Jarvelin, Marjo-Riitta, Jornsten, Rebecka, Langston, Michael A., Ramasamy, Adaikalavan, Rogers, Gary, Wang, Hui and Benson, Mikael (2012) Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms. Genome Biology, 13 6: R46.1-R46.9. doi:10.1186/gb-2012-13-6-r46


Author Barrenas, Fredrik
Chavali, Sreenivas
Couto Alves, Alexessander
Coin, Lachlan
Jarvelin, Marjo-Riitta
Jornsten, Rebecka
Langston, Michael A.
Ramasamy, Adaikalavan
Rogers, Gary
Wang, Hui
Benson, Mikael
Title Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms
Journal name Genome Biology   Check publisher's open access policy
ISSN 1474-7596
1474-760X
Publication date 2012-06-15
Year available 2012
Sub-type Article (original research)
DOI 10.1186/gb-2012-13-6-r46
Open Access Status DOI
Volume 13
Issue 6
Start page R46.1
End page R46.9
Total pages 9
Place of publication London, United Kingdom
Publisher BioMed Central
Language eng
Formatted abstract
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. 
Keyword Biotechnology & Applied Microbiology
Genetics & Heredity
Biotechnology & Applied Microbiology
Genetics & Heredity
BIOTECHNOLOGY & APPLIED MICROBIOLOGY
GENETICS & HEREDITY
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID 223367
R01-AA-018776
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
 
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