Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Jul 12;26(1):661.
doi: 10.1186/s12864-024-11076-6.

Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries

Zixuan Yu  1 , Salma Abdel-Azim  1 , Priya Duggal  1 , Candelaria Vergara  2
Affiliations

Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries

Zixuan Yu et al. BMC Genomics. .

Abstract

Background: Acute infection with hepatitis C virus (HCV) affects millions of individuals worldwide. Host genetics plays a role in spontaneous clearance of the acute infection which occurs in approximately 30% of the individuals. Common variants in GPR158, genes in the interferon lambda (IFNL) cluster, and the Major Histocompatibility complex (MHC) region have been associated with HCV clearance in populations of diverse ancestry. Fine mapping of those regions has identified some key variants and amino acids as potential causal variants but the role of rare variants in those regions and in the genome, in general, has not been explored. We aimed to detect haplotypes containing rare variants related to HCV clearance using identity-by-descent (IBD) haplotype sharing between unrelated cases-case pairs and case-controls pairs in 1,739 individuals of European ancestry and 1,869 African Americans. Additionally, we aimed to detect ancestry-specific effects in African Americans using local ancestry mapping.

Results: We detected 2,370,341 and 1,567,748 individual pairs of IBD segments in the individuals of European ancestry and African Americans, respectively. Individuals of European descent had more segments of longer length compared to African Americans. We did not detect any significant IBD signals in the known associated or new gene regions. We also failed to detect any significant genome-wide local ancestry signals in the African Americans.

Conclusions: IBD is based on sharing of haplotypes and is most powerful in populations with a shared founder or recent common ancestor. For the complex trait of HCV clearance, we used two outbred, global populations that limited our power to detect IBD associations. Overall, in these population-based samples we failed to detect rare variations associated with HCV clearance in individuals of European ancestry and African Americans, and we didn't detect local ancestry-specific effects associated with HCV clearance in African Americans with our current sample size.

Keywords: GWAS; HCV clearance; IBD mapping; Rare variants; Unrelated individuals.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethics approval and consent to participate: All subjects gave written informed consent for this study. Each individual study obtained consent for genetic testing from their governing Institutional Review Board (IRB) and the Johns Hopkins School of Medicine Institutional Review Board approved the overall analysis. All methods were performed with the relevant guidelines and regulations in accordance with the Declaration of Helsinki. Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Density plots of the lengths of detected IBD segments in individuals with HCV clearance and persistence from samples of European ancestry and admixed African Americans. IBD segments > 8 cM are not shown
Fig. 2
Fig. 2
Manhattan plot of the P values obtained using IBD permutation analysis in African Americans (Upper Panel) and individuals of European ancestry (Lower Panel). The blue line indicates the genome-wide threshold for each population and the black line is the minimal permutation value obtainable with 5 million permutations (2 × 10–7). Each dot corresponds to the P value of a genetic marker. Chromosome coordinates are based on GRCh37/hg19 built
Fig. 3
Fig. 3
Manhattan plots summarizing the results of the association of local African ancestry and HCV clearance in 1,869 admixed African American individuals (1529 with HCV persistence/340 with HCV clearance). Each point corresponds to the P value for a marker representing a local ancestry window estimated by RFMIX v2. The P values are plotted by location of the markers across the genome. The red line represents the level genome-wide significance (P value = 1.80 × 10–5). No markers exceeded the significance threshold
See this image and copyright information in PMC

Update of

Similar articles

See all similar articles

References

    1. Barathan M, Mohamed R, Yong YK, Kannan M, Vadivelu J, Saeidi A, Larsson M, Shankar EM. Viral Persistence and Chronicity in Hepatitis C Virus Infection: Role of T-Cell Apoptosis, Senescence and Exhaustion. Cells. 2018;7(10):165. 10.3390/cells7100165. - PMC - PubMed
    1. Larrubia JR, Moreno-Cubero E, Lokhande MU, Garcia-Garzon S, Lazaro A, Miquel J, Perna C, Sanz-de-Villalobos E. Adaptive immune response during hepatitis C virus infection. World J Gastroenterol. 2014;20(13):3418–30. - PMC - PubMed
    1. Thomas DL, Astemborski J, Rai RM, Anania FA, Schaeffer M, Galai N, Nolt K, Nelson KE, Strathdee SA, Johnson L, Laeyendecker O, Boitnott J, Wilson LE, Vlahov D. The natural history of hepatitis C virus infection: host, viral, and environmental factors. JAMA. 2000;284(4):450–6. - PubMed
    1. Hajarizadeh B, Grebely J, Dore GJ. Epidemiology and natural history of HCV infection. Nat Rev Gastroenterol Hepatol. 2013;10(9):553–62. - PubMed
    1. Micallef JM, Kaldor JM, Dore GJ. Spontaneous viral clearance following acute hepatitis C infection: a systematic review of longitudinal studies. J Viral Hepat. 2006;13(1):34–41. - PubMed