title: Admixture analysis of spontaneous hepatitis C virus clearance in individuals of African descent.
abstract: Hepatitis C virus (HCV) infects an estimated 3% of the global population with the majority of individuals (75-85%) failing to clear the virus without treatment, leading to chronic liver disease. Individuals of African descent have lower rates of clearance compared with individuals of European descent and this is not fully explained by social and environmental factors. This suggests that differences in genetic background may contribute to this difference in clinical outcome following HCV infection. Using 473 individuals and 792,721 single-nucleotide polymorphisms (SNPs) from a genome-wide association study (GWAS), we estimated local African ancestry across the genome. Using admixture mapping and logistic regression, we identified two regions of interest associated with spontaneous clearance of HCV (15q24, 20p12). A genome-wide significant variant was identified on chromosome 15 at the imputed SNP, rs55817928 (P=6.18 × 10(-8)) between the genes SCAPER and RCN. Each additional copy of the African ancestral C allele is associated with 2.4 times the odds of spontaneous clearance. Conditional analysis using this SNP in the logistic regression model explained one-third of the local ancestry association. Additionally, signals of selection in this area suggest positive selection due to some ancestral pathogen or environmental pressure in African, but not in European populations.
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: G L
authors.initials: GL
authors.lastname: Wojcik
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Thio
authors.affiliation: 1] Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA [2] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: W H L
authors.initials: WH
authors.lastname: Kao
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: R
authors.initials: R
authors.lastname: Latanich
authors.affiliation: Infections and Immunoepidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD, USA.
authors.forename: J J
authors.initials: JJ
authors.lastname: Goedert
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: S H
authors.initials: SH
authors.lastname: Mehta
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: G D
authors.initials: GD
authors.lastname: Kirk
authors.affiliation: Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
authors.forename: M G
authors.initials: MG
authors.lastname: Peters
authors.affiliation: Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: A L
authors.initials: AL
authors.lastname: Cox
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: A Y
authors.initials: AY
authors.lastname: Kim
authors.affiliation: Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
authors.forename: R T
authors.initials: RT
authors.lastname: Chung
authors.affiliation: 1] Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA [2] Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
authors.forename: D L
authors.initials: DL
authors.lastname: Thomas
authors.affiliation: Department of Epidemiology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD, USA.
authors.forename: P
authors.initials: P
authors.lastname: Duggal
mesh_terms: D000483:Alleles; D044383:Black People / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics; D002890:Chromosomes, Human, Pair 20 / Q000235:genetics; D005260:Female; D055106:Genome-Wide Association Study; D019698:Hepatitis C, Chronic / Q000208:ethnology / Q000235:genetics*; D006801:Humans; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012075:Remission, Spontaneous
chemical_list: D002352:Carrier Proteins; C523211:SCAPER protein, human