Meta-Analysis And Biologiical Pathway Gsea Research Of Lung Cancer GWAS Data

As one of the most serious deadly disease around the world, lung cancer is seriously threating the human health today. So it is become more and more urgent to ascertain the pathogenesis of lung cancer. The same as many other serious diseases,such as tumour, diabetes, cardiovascular disease, Alzheimer’s disease and so on, lung cancer belongs to a particular category of illness which is called complex disease.Comparing with the monogenic disease, an attack of this complex disease involves the combined action of relevant genes, and each of their influence on the disease is different and very minor, which make it difficult to research this complex disease by using the traditional method.An effective method to research the complex disease is genome wide association study(GWAS), which created by Klein et al. when they were researching the macular degeneration in 2005. GWAS can find the SNP sites associated with a certain disease in the range of whole genome. However, because of the different sample scales and heterogeneity among different races, the result of different GWAS researches for one disease may be inconsistent. Therefore, to get a more reliable conclusion, meta-analysis be used to comprehensively assess and modify the GWAS result.Even so, the result of GWAS and meta-analysis is merely the single SNP sites associated with a certain disease, which is far away from the essence of the disease pathogenesis. Gene set enrichment analysis(GSEA) can find some biological pathways associated with a certain disease by calculating the SNP sites which are from GWAS and meta-analysis. These biological pathways information are more directly associated with the essence of disease pathogenesis.In this paper, we collected all of the lung cancer GWAS researches from GRASP v2.0 database, and performed an meta-analysis on rs1051730 SNP site which is most frequently studied by these GWAS researches and the results are inconsistent. And then,we calculated the results of GWAS and meta-analysis by using the GSEA method to find biological pathways associated with lung cancer. Finally, we analyzed these biological pathways to discover the pathogenesis of lung cancer.The result showed that(1) rs1051730 SNP is significantly associate with lung cancer both on the whole population and on the subgroup including Asian, European,African populations.(2) One of lung cancer pathogenesis is the abnormity of acetylcholine receptor and acetylcholine-activated cation-selective channel activity. This abnormity will result in the downstream pathways activation, which is like the process of interaction between nicotine(or nitrosamine compounds) and acetylcholine receptor,and lead to lung cancer formation. Moreover, we also found that the abnormity of singletransduction and identical protein binding may be associated with lung cancer. These discoveries will be useful to clinic treatment and drug design of lung cancer in the future.