原创力文档shared molecular and functional frameworks among five complex human disorders a comparative study on interactomes linked to susceptibility genes共享分子和功能框架中五个人类复杂疾病interactomes与易感基因的比较研究.pdfVIP
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shared molecular and functional frameworks among five complex human disorders a comparative study on interactomes linked to susceptibility genes共享分子和功能框架中五个人类复杂疾病interactomes与易感基因的比较研究
Shared Molecular and Functional Frameworks among
Five Complex Human Disorders: A Comparative Study on
Interactomes Linked to Susceptibility Genes
Ramesh Menon1,2, Cinthia Farina1,2*
1 Neuroimmunology and Neuromuscular Disorders Unit, Foundation IRCCS Neurological Institute Carlo Besta, Milan, Italy, 2 Institute of Experimental Neurology (INSpe),
San Raffaele Scientific Institute, Milan, Italy
Abstract
Background: Genome-wide association studies (gwas) are invaluable in revealing the common variants predisposing to
complex human diseases. Yet, until now, the large volumes of data generated from such analyses have not been explored
extensively enough to identify the molecular and functional framework hosting the susceptibility genes.
Methodology/Principal Findings: We investigated the relationships among five neurodegenerative and/or autoimmune
complex human diseases (Parkinson’s disease-Park, Alzheimer’s disease-Alz, multiple sclerosis-MS, rheumatoid arthritis-RA and
Type 1 diabetes-T1D) by characterising the interactomes linked to their gwas-genes. An initial study on the MS interactome
indicated that several genes predisposing to the other autoimmune or neurodegenerative disorders may come into contact
with it, suggesting that susceptibility to distinct diseases may converge towards common molecular and biological networks.
In order to test this hypothesis, we performed pathway enrichment analyses on each disease interactome independently.
Several issues related to immune function and growth factor signalling pathways appeared in all autoimmune diseases, and,
surprisingly, in Alzheimer’s disease. Furthermore, the paired analyses of disease interactomes revealed significant molecular
and functional relatedness among autoimmune diseases, and, unexpectedly, between T1D and Alz.
Conclusions/Significance: The systems biology approach highlighted several known
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