期刊
JOURNAL OF CANCER
卷 12, 期 3, 页码 840-848出版社
IVYSPRING INT PUBL
DOI: 10.7150/jca.47918
关键词
MetaXcan; cervical cancer; transcriptome-wide association study; Gene expression level; associated genes
类别
资金
- Natural Science Foundation of Jiangsu Province [BK20181472]
- Youth Foundation of Humanity and Social Science - Ministry of Education of China [18YJC910002]
- China Postdoctoral Science Foundation [2018M630607, 2019T120465]
- QingLan Research Project of Jiangsu for Outstanding Young Teachers
- Six-Talent Peaks Project in Jiangsu Province of China [WSN-087]
- Social Development Project of Xuzhou
- Postdoctoral Science Foundation of Xuzhou Medical University
- National Natural Science Foundation of China [81402765]
- National Bureau of Statistics of China [2014LY112]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX20_2501]
- Training Project for Youth Science and Technology Innovation Team at Xuzhou Medical University
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD) for Xuzhou Medical University
The study integrated GWAS and gene expression data to identify multiple genes associated with cervical cancer, validated in European and East Asian populations. Co-expression and protein-protein interaction analysis revealed interactions between these genes. The results suggest that four non-MHC genes may be causally associated with cervical cancer risk.
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.
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