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. 2024 Jun;32(6):708-716.
doi: 10.1038/s41431-023-01521-7. Epub 2024 Jan 10.

Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections

Sally N Adebamowo  1   2 , Adebowale Adeyemo  3 , Amos Adebayo  4 , Peter Achara  5 , Bunmi Alabi  6 , Rasheed A Bakare  7 , Ayotunde O Famooto  8 , Kayode Obende  9 , Richard Offiong  10 , Olayinka Olaniyan  11 , Sanni Ologun  12 , Charles Rotimi  3 ; ACCME Research Group as part of the H3Africa Consortium; Clement A Adebamowo  13   14   15
Collaborators, Affiliations

Genome, HLA and polygenic risk score analyses for prevalent and persistent cervical human papillomavirus (HPV) infections

Sally N Adebamowo et al. Eur J Hum Genet. 2024 Jun.

Abstract

Genetic variants that underlie susceptibility to cervical high-risk human papillomavirus (hrHPV) infections are largely unknown. We conducted discovery genome-wide association studies (GWAS), replication, meta-analysis and colocalization, generated polygenic risk scores (PRS) and examined the association of classical HLA alleles and cervical hrHPV infections in a cohort of over 10,000 women. We identified genome-wide significant variants for prevalent hrHPV around LDB2 and for persistent hrHPV near TPTE2, SMAD2, and CDH12, which code for proteins that are significantly expressed in the human endocervix. Genetic variants associated with persistent hrHPV are in genes enriched for the antigen processing and presentation gene set. HLA-DRB1*13:02, HLA-DQB1*05:02 and HLA-DRB1*03:01 were associated with increased risk, and HLA-DRB1*15:03 was associated with decreased risk of persistent hrHPV. The analyses of peptide binding predictions showed that HLA-DRB1 alleles that were positively associated with persistent hrHPV showed weaker binding with peptides derived from hrHPV proteins and vice versa. The PRS for persistent hrHPV with the best model fit, had a P-value threshold (PT) of 0.001 and a p-value of 0.06 (-log10(0.06) = 1.22). The findings of this study expand our understanding of genetic risk factors for hrHPV infection and persistence and highlight the roles of MHC class II molecules in hrHPV infection.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Miami plot for meta-analysis of ACCME and PACS cohorts for prevalent and persistent high-risk HPV.
Fig. 2
Fig. 2
Distribution of binding affinity IC50 values by HLA-DRB1 allele category (A) all binding predictions (B) Excluding non-binders (lC50 > 5000 nM).
Fig. 3
Fig. 3
Polygenic Risk Score on predicted risk of prevalent and persistent HPV.
See this image and copyright information in PMC

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