Journal
GENETIC EPIDEMIOLOGY
Volume 46, Issue 7, Pages 463-474Publisher
WILEY
DOI: 10.1002/gepi.22490
Keywords
epistasis; HLA; Mycobacterium tuberculosis; nearest-neighbor feature selection; resistance to infection; sarcoidosis
Funding
- Bill and Melinda Gates Foundation
- National Institutes of Health
- Foundation for Sarcoidosis Research
Ask authors/readers for more resources
This study investigates the association between human leukocyte antigen (HLA) alleles and the occurrence and severity of tuberculosis and sarcoidosis in individuals of African ancestry. The findings reveal similarities in the effects of HLA-DRB1, -DQB1, and -DPB1 alleles on resistance to tuberculosis and persistent sarcoidosis.
Tuberculosis and sarcoidosis are inflammatory diseases characterized by granulomas that may occur in any organ but are often found in the lung. The panoply of classical human leukocyte antigen (HLA) alleles associated with occurrence and/or severity of both diseases varies considerably across studies. This heterogeneity of results, due to variation in factors like ancestry and disease subphenotype, as well as the use of simple modeling strategies to elucidate likely complex relationships, has made conclusions about underlying commonalities difficult. Here we perform HLA association analyses in individuals of African ancestry, using a greater resolution to include subphenotypes of disease and employing more comprehensive analytical techniques. Using a novel application of nearest-neighbor feature selection to score allelic importance, we investigated HLA allele association with Mycobacterium tuberculosis exposure outcomes in the first analysis of both latent Mycobacterium tuberculosis infection and active disease compared with those who, despite long-term exposure to active index cases, have neither positive diagnostic tests nor display clinical symptoms. We also compared persistent to resolved sarcoidosis. This led to the identification of novel HLA associations and evidence of main effects and interaction effects. We found strikingly similar main effects and interaction effects at HLA-DRB1, -DQB1, and -DPB1 in those resistant to tuberculosis (either latent or active) and persistent sarcoidosis.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available