highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms高度相互关联的基因在特定疾病网络丰富的疾病有关的多态性.pdfVIP

Barrenäs et al. Genome Biology 2012, 13:R46 /2012/13/6/R46 RESEARCH Open Access Highly interconnected genes in disease-specific networks are enriched for disease-associated polymorphisms 1† 2† 3 3 3,4 Fredrik Barrenäs , Sreenivas Chavali , Alexessander Couto Alves , Lachlan Coin , Marjo-Riitta Jarvelin , 5 6 3,7 6 1 Rebecka Jörnsten , Michael A Langston , Adaikalavan Ramasamy , Gary Rogers , Hui Wang and Mikael Benson1,8* 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-mediate