Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries
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...
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2025-07-01
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| Online Access: | https://doi.org/10.1186/s12864-024-11076-6 |
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| author | Zixuan Yu Salma Abdel-Azim Priya Duggal Candelaria Vergara |
| author_facet | Zixuan Yu Salma Abdel-Azim Priya Duggal Candelaria Vergara |
| author_sort | Zixuan Yu |
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| description | 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. |
| format | Article |
| id | doaj-art-93167ceabe094fb9ae14bfef1840a6c8 |
| institution | Kabale University |
| issn | 1471-2164 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Genomics |
| spelling | doaj-art-93167ceabe094fb9ae14bfef1840a6c82025-08-20T03:45:47ZengBMCBMC Genomics1471-21642025-07-012611910.1186/s12864-024-11076-6Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestriesZixuan Yu0Salma Abdel-Azim1Priya Duggal2Candelaria Vergara3Johns Hopkins University, Bloomberg School of Public HealthJohns Hopkins University, Bloomberg School of Public HealthJohns Hopkins University, Bloomberg School of Public HealthJohns Hopkins University, Bloomberg School of Public HealthAbstract 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.https://doi.org/10.1186/s12864-024-11076-6IBD mappingHCV clearanceRare variantsGWASUnrelated individuals |
| spellingShingle | Zixuan Yu Salma Abdel-Azim Priya Duggal Candelaria Vergara Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries BMC Genomics IBD mapping HCV clearance Rare variants GWAS Unrelated individuals |
| title | Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries |
| title_full | Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries |
| title_fullStr | Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries |
| title_full_unstemmed | Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries |
| title_short | Identity by descent and local ancestry mapping of HCV spontaneous clearance in populations of diverse ancestries |
| title_sort | identity by descent and local ancestry mapping of hcv spontaneous clearance in populations of diverse ancestries |
| topic | IBD mapping HCV clearance Rare variants GWAS Unrelated individuals |
| url | https://doi.org/10.1186/s12864-024-11076-6 |
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