Study On Gene Regulatory Network Of Complex Disease Based On GWAS

Explaining the causes of common and complex diseases is a major challenge in genetic research.Similar to other complex diseases,major breakthroughs in the interpretation of the high heritability of complex diseases through genome-wide association analysis remain elusive.To overcome this dilemma,genetic research on complex diseases has adopted various strategies,such as the formation of large-scale alliances to increase sample size and sequencing methods.Here,we advocate starting from genome-wide association analysis,map risk genes associated with complex diseases into protein interaction networks,and explore the interaction of bipolar genes.To find core core genes,we introduced network analysis after genome-wide association analysis.Then we built a gene regulatory network research based on genome-wide association analysis of complex diseases into a pipeline and verified it with Alzheimer's disease.Experiments have proved that network-assisted research methods are helpful to study the pathogenesis of complex diseases.It can be used as a high-level analysis after genome-wide association studies.Then,we used this analysis pipeline to analyze the gene interactions of bipolar disorder.A total of 482,247 single-nucleotide polymorphism site data related to bipolar disorder were downloaded from the WTCCC,and 6,458 risk single-nucleotide polymorphisms were obtained according to data quality control and other conditions.Single nucleotide polymorphisms were mapped to the gene method and 2,045 risk genes were obtained.After gene enrichment analysis,the risk genes obtained were mapped to a protein-protein interaction network,and 112 risk genes with a degree greater than 17 were found,15 of which were duplicates of previously reported disease-associated important genes.Although the underlying genes have not been reported,most genes have been reported to be related to other brain diseases,neurological diseases,and cardiovascular diseases.A modular analysis of the core genes revealed five important modules and four core pivotal genes(FBXL13,WDFY2,bFGF,and MTHFD1L).Examining the interrelated components of the 4 modules and the functional enrichment analysis revealed the biological significance of the risk of bipolar disorder.These core genes have not yet been reported to be directly related to BD,but may function by interacting with genes directly related to BD.Our approach yields new ideas for finding genes that are indirectly related to complex diseases but are important.