Individuals of African ancestry share HLA alleles protective against tuberculosis and sarcoidosis
Dawkins BA, Garman L, Cejda N, Pezant N, Rasmussen A, Rybicki BA, Levin AM, Benchek P, Hawn TR, Seshadri C, Iannuzzi MC, Stein CM, and Montgomery CG. Individuals of african ancestry share HLA alleles protective against tuberculosis and sarcoidosis. Genetic Epidemiology 2021; 45(7):751-752.
Tuberculosis (TB) and sarcoidosis are distinct granulomatous disorders with numerous genetic associations. Human leukocyte antigen (HLA) is important in susceptibility and progression in both diseases. Although TB is caused by Mycobacterium tuberculosis, HLA associations in case control TB studies are highly variable, potentially due to phenotype heterogeneity, limited allelic resolution, and narrow analytical methods that exclude more complex associations common to biological data. Using four digit HLA alleles and applying more inclusive feature selection methodology, we provide the first HLA association analysis in TB that compares latent and active TB to individuals who display no evidence of infection and maintain negative diagnostic tests over a long term period of exposure to individuals with active TB. To detect a more comprehensive array of statistical effects, we introduce a novel application of nearest neighbor feature selection that uses a consensus approach across three input neighborhood algorithms to define allelic importance for classifying outcomes. This nearest neighbor approach is generally applicable in the context of binary classification and regression, with either categorical or continuous predictors. We compare our findings to sarcoidosis, both persistent and resolving. We provide the first comparison between TB and sarcoidosis resistance phenotypes, showing that HLA-DRB1 alleles ∗01:02, ∗03:02, ∗12:01, and ∗13:02 are associated with both resolving sarcoidosis in African Americans and long term resistance to latent or active TB in Ugandans.