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Genome-wide association study of chronic hepatitis B virus infection reveals a novel candidate risk allele on 11q22.3
  1. Ahmed Al-Qahtani1,2,
  2. Hanif G Khalak3,
  3. Fowzan S Alkuraya4,5,6,
  4. Waleed Al-hamoudy2,7,
  5. Khalid Alswat2,7,
  6. Mohammed A Al Balwi8,9,10,
  7. Ibrahim Al AbdulKareem8,10,
  8. Faisal M Sanai2,11,
  9. Ayman A Abdo2,7,12
  1. 1Department of Infection and Immunity, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
  2. 2Liver Disease Research Center, King Saud University, Riyadh, Saudi Arabia
  3. 3Department of Computational Genetics, Weill Cornell Medical College, Doha, Qatar
  4. 4Department of Genetics, Research Center, King Faisal Specialist Hospital & Research Center, Riyadh, Saudi Arabia
  5. 5Department of Anatomy and Cell Biology, College of Medicine, Alfaisal University, Riyadh, Saudi Arabia
  6. 6Department of Pediatrics, College of Medicine, King Saud University, Riyadh, Saudi Arabia
  7. 7Division of Gastroenterology, Department of Medicine, King Saud University, Riyadh, Saudi Arabia
  8. 8King Abdullah International Medical Research Center, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
  9. 9Department of Pathology and Laboratory Medicine, King Abdulaziz Medical City, Riyadh, Saudi Arabia
  10. 10College of Medicine, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia
  11. 11Department of Hepatobiliary Sciences & Liver Transplantation, King Abdulaziz Medical City, Riyadh, Saudi Arabia
  12. 12Department of Medicine, University of Calgary, Calgary, Alberta, Canada
  1. Correspondence to Dr Ayman Abdo, Division of Gastroenterology, Department of Medicine, King Saud University, PO Box 2925 (59), Riyadh 11461, Saudi Arabia; aabdo{at}ksu.edu.sa

Abstract

Background Hepatitis B virus (HBV) affects millions of people worldwide. While some people are able to clear the virus following the first encounter, those who develop chronic infection manifest remarkable clinical heterogeneity that ranges from asymptomatic carrier state to cirrhosis and hepatocellular carcinoma. Despite extensive studies, little is known about genetic host factors that influence the outcome of chronic HBV infection. Thus, we conducted this study to investigate the genetic risk of developing active liver disease among chronic carriers of HBV.

Methods In this study, we conducted a genome-wide association study (GWAS) on a cohort of patients with chronic HBV infection.

Results One particular SNP that is 16 kb upstream of Ferredoxin 1 was found to have an association with complicated chronic HBV infection (cirrhosis and hepatocellular carcinoma) that reached GWAS significance, and was successfully validated on an independent set of samples.

Conclusions This first GWAS in an Arab population further demonstrates the utility of this approach in elucidating the genetic risk of HBV infection-related complications and highlights the advantage of conducting GWAS in different ethnicities to achieve that goal.

  • hepatocellular carcinoma
  • cirrhosis
  • Ferredoxin
  • Arab
  • GWAS

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