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

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 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 3,608 individuals with European and African ancestry. RESULTS: We detected 1,711,832 and 5,678,043 and individual pairs of IBD segments in the European and African ancestry individuals, respectively. As expected, individuals of African descent had more, and shorter segments compared to Europeans. We did not detect any significant IBD signals in the known associated gene regions. 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 this population-based sample we failed to detect rare variations associated with HCV clearance in individuals of European and African ancestry.