Admixture Mapping in African Americans Identifies New Risk Loci for HCV-Related Cirrhosis. Clin Gastroenterol Hepatol 2023 Apr;21(4):1023-1030.e39
Date
06/10/2022Pubmed ID
35680035Pubmed Central ID
PMC9722981DOI
10.1016/j.cgh.2022.05.020Scopus ID
2-s2.0-85135349654 (requires institutional sign-in at Scopus site)Abstract
BACKGROUND & AIMS: Cirrhosis is the main predisposing condition for hepatocellular carcinoma. Host genetic risk factors have been reported for cirrhosis; however, whether there is a genetic contribution to racial disparities in cirrhosis requires further investigation.
METHODS: We used an affected-only mapping by admixture linkage disequilibrium analysis to characterize the genetic risk of cirrhosis in 227 African American patients with cirrhosis genotyped at 19,804 ancestry-informative marker single nucleotide polymorphisms. We additionally performed analyses stratified by hepatitis C virus (HCV) infection status. To replicate our findings, we conducted a case-control analysis in an external study population (452 cases and 196 controls).
RESULTS: The mean age of patients was 63.3 years and 98.2% were male. Risk factors for cirrhosis included HCV infection (83.7%) and alcohol abuse (56.4%). In the admixture mapping analysis, we found that European ancestry on chromosome 2q21.1 and African ancestry on chromosome 6p21.2 were associated with increased risk of cirrhosis in African Americans. In the fine-mapping analysis, we identified regions near POTEKP on 2q21.1 (P = .0001) and DNAH8 on 6p21.2 (P = .0017) that were associated with cirrhosis. As the admixture peaks in the HCV-positive patients were the same as those in the overall group, findings in the analysis are reflective of the HCV-positive group. In the replication analysis, the results on chromosome 2 were not significant after adjusting for multiple comparisons, and we could not replicate the results on chromosome 6.
CONCLUSIONS: We used admixture mapping to identify novel genomic regions on 2q21.1 and 6p21.2 that may be associated with HCV-related cirrhosis risk in African Americans.
Author List
Kim HS, Shetty PB, Tsavachidis S, Dong J, Amos CI, El-Serag HB, Thrift APAuthor
Jing Dong PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Chromosome MappingFemale
Genotype
Hepacivirus
Hepatitis C
Humans
Liver Cirrhosis
Male
Middle Aged
Polymorphism, Single Nucleotide
