@article{1d26fec927f04f2b930f76d9ac2f23e2,
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.",
author = "Wojcik, {G. L.} and Thio, {C. L.} and Kao, {W. H.L.} and R. Latanich and Goedert, {J. J.} and Mehta, {S. H.} and Kirk, {G. D.} and Peters, {M. G.} and Cox, {A. L.} and Kim, {A. Y.} and Chung, {R. T.} and Thomas, {D. L.} and P. Duggal",
note = "Funding Information: Primary data are available through the central NIH GWAS data repository at the National Center for Biotechnology Information (NCBI), National Library of Medicine (http://grants.nih.gov/grants/guide/notice-files/NOT-OD-07-088.html). This project was funded in whole or in part by the Office of AIDS Research through the Center for Inherited Diseases at Johns Hopkins University, the National Institute on Drug Abuse (R01DA013324, DA033541, DA012568 and DA04334), the National Institute of Allergy and Infectious Diseases (U19AI088791 and AI082630), and the Frederick National Laboratory for Cancer Research (contract HHSN261200800001E). This research was supported in part by the Intramural Research Programs of the National Institutes of Health and the Frederick National Laboratory for Cancer Research. The WIHS is funded by the National Institute of Allergy and Infectious Diseases (UO1-AI-35004, UO1-AI-31834, UO1-AI-34994, UO1-AI-34989, UO1-AI-34993 and UO1-AI-42590) and by the Eunice Kennedy Shriver National Institute of Child Health and Human Development (UO1-HD-32632). The study is co-funded by the National Cancer Institute, the National Institute on Drug Abuse, and the National Institute on Deafness and Other Communication Disorders. Funding is also provided by the National Center for Research Resources (UCSF-CTSI Grant Number UL1 RR024131). The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, nor does mention of trade names, commercial products, or organizations imply endorsement by the US Government. This Research was supported in part by the Intramural Research Program of the NIH, Frederick National Lab, Center for Cancer Research.",
year = "2014",
month = jun,
doi = "10.1038/gene.2014.11",
language = "English (US)",
volume = "15",
pages = "241--246",
journal = "Genes and immunity",
issn = "1466-4879",
publisher = "Nature Publishing Group",
number = "4",
}