Laisk, Triin, juhendajaKoel, Mariann, juhendajaBartlett, Ksenia Chloe2023-06-152023-06-152023https://hdl.handle.net/10062/90632Cervical cancer is a significant health concern linked to high-risk human papillomavirus (HPV) infection. This study aimed to explore the genetic susceptibility factors associated with high-risk HPV infection using a genome-wide association study (GWAS) approach. The analysis included 3445 cases and 10467 controls, utilizing women with positive high- risk or potentially high-risk HPV test results as cases and those without as controls. The GWAS analysis identified a locus for high-risk HPV infection within the MHC region on chromosome 6p21.3. To further elucidate the specific human leukocyte antigen (HLA) alleles associated with high-risk HPV infection, the signal was mapped, revealing HLA- DQB10603, HLA-DRB11301, HLA-DRB113, HLA-DQA10103, HLA-DQB10602, and HLA-DRB113 as the most significantly associated alleles. In addition, the study identified 15 diagnosis codes with significantly different prevalences in cases and controls, indicating associations between high-risk HPV infection and viral agents, abnormal findings in female genital specimens, malignant neoplasm of the cervix uteri, and other sexually transmitted diseases. Several limitations were encountered, including the absence of a specific code for high-risk HPV infection, which affected sample identification and size. The lack of a replication co- hort necessitates further validation in independent datasets. Furthermore, the transient na- ture of most HPV infections posed challenges in distinguishing controls with no high-risk HPV infection history. In conclusion, this research highlights the need for larger GWAS studies to investigate the genetics of high-risk HPV infection comprehensively. Discovering additional genetic sus- ceptibility factors can enhance prevention strategies and contribute to advancements in per- sonalized medicine.engopenAccessAttribution-NonCommercial-NoDerivatives 4.0 Internationalcervical cancerhigh-risk human papillomavirus infectiongenetic susceptibility factorsgenome-wide association studyhuman leukocyte antigen (HLA)MHC regionThesis