J Cancer 2021; 12(3):840-848. doi:10.7150/jca.47918

Research Paper

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

Haimiao Chen1#, Ting Wang1#, Shuiping Huang1,2✉, Ping Zeng1,2✉

1. Department of Epidemiology and Biostatistics, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
2. Center for Medical Statistics and Data Analysis, School of Public Health, Xuzhou Medical University, Xuzhou, Jiangsu, 221004, China.
#These authors contributed equally to this work.

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Citation:
Chen H, Wang T, Huang S, Zeng P. New novel non-MHC genes were identified for cervical cancer with an integrative analysis approach of transcriptome-wide association study. J Cancer 2021; 12(3):840-848. doi:10.7150/jca.47918. Available from https://www.jcancer.org/v12p0840.htm

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Abstract

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 (N = 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. WDR19, RP11-384K6.2, RP11-384K6.6 and ITSN1). Further, we attempted to validate our results in another independent cervical cancer GWAS from the East Asian population (N = 3,314) and re-discovered four genes including WDR19, HLA-DOB, MICB and OR2B8P. In our subsequent co-expression analysis, we discovered SLAMF7 and LTA were co-expressed in TCGA tumor samples and showed both WDR19 and ITSN1 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.

Keywords: MetaXcan, cervical cancer, transcriptome-wide association study, Gene expression level, associated genes