New novel non-MHC genes were identified for cervical cancer with an integrative analysis approach of transcriptome-wide association study.

Although genome-wide association studies (GWAS) have successfully identified multiple genetic variants associated with cervical cancer, the functional role of those variants is not well understood. To bridge such gap, we integrated the largest cervical cancer GWAS ( = 9,347) with gene expression measured in six human tissues to perform a multi-tissue transcriptome-wide association study (TWAS). We identified a total of 20 associated genes in the European population, especially four novel non-MHC genes (i.e. , , and ). Further, we attempted to validate our results in another independent cervical cancer GWAS from the East Asian population ( = 3,314) and re-discovered four genes including , , and . In our subsequent co-expression analysis, we discovered and were co-expressed in TCGA tumor samples and showed both and were enriched in "plasma membrane". Using the protein-protein interaction analysis we observed strong interactions between the proteins produced by genes that are associated with cervical cancer. Overall, our study identified multiple candidate genes, especially four non-MHC genes, which may be causally associated with the risk of cervical cancer. However, further investigations with larger sample size are warranted to validate our findings in diverse populations.