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Genome-wide association study of prevalent and persistent cervical high-risk human papillomavirus (HPV) infection.

BMC Medical Genetics 2020 November 24
BACKGROUND: Genetic factors may influence the susceptibility to high-risk (hr) human papillomavirus (HPV) infection and persistence. We conducted the first genome-wide association study (GWAS) to identify variants associated with cervical hrHPV infection and persistence.

METHODS: Participants were 517 Nigerian women evaluated at baseline and 6 months follow-up visits for HPV. HPV was characterized using SPF10 /LiPA25 . hrHPV infection was positive if at least one carcinogenic HPV genotype was detected in a sample provided at the baseline visit and persistent if at least one carcinogenic HPV genotype was detected in each of the samples provided at the baseline and follow-up visits. Genotyping was done using the Illumina Multi-Ethnic Genotyping Array (MEGA) and imputation was done using the African Genome Resources Haplotype Reference Panel. Association analysis was done for hrHPV infection (125 cases/392 controls) and for persistent hrHPV infection (51 cases/355 controls) under additive genetic models adjusted for age, HIV status and the first principal component (PC) of the genotypes.

RESULTS: The mean (±SD) age of the study participants was 38 (±8) years, 48% were HIV negative, 24% were hrHPV positive and 10% had persistent hrHPV infections. No single variant reached genome-wide significance (p < 5 X 10- 8 ). The top three variants associated with hrHPV infections were intronic variants clustered in KLF12 (all OR: 7.06, p = 1.43 × 10- 6 ). The top variants associated with cervical hrHPV persistence were in DAP (OR: 6.86, p = 7.15 × 10- 8 ), NR5A2 (OR: 3.65, p = 2.03 × 10- 7 ) and MIR365-2 (OR: 7.71, p = 2.63 × 10- 7 ) gene regions.

CONCLUSIONS: This exploratory GWAS yielded suggestive candidate risk loci for cervical hrHPV infection and persistence. The identified loci have biological annotation and functional data supporting their role in hrHPV infection and persistence. Given our limited sample size, larger discovery and replication studies are warranted to further characterize the reported associations.

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