Multi-ancestry meta-analysis of host genetic susceptibility to tuberculosis identifies shared genetic architecture.

ABSTRACT: The heritability of susceptibility to tuberculosis (TB) disease has been well recognized. Over 100 genes have been studied as candidates for TB susceptibility, and several variants were identified by genome-wide association studies (GWAS), but few replicate. We established the International Tuberculosis Host Genetics Consortium to perform a multi-ancestry meta-analysis of GWAS, including 14,153 cases and 19,536 controls of African, Asian, and European ancestry. Our analyses demonstrate a substantial degree of heritability (pooled polygenic h² = 26.3%, 95% CI 23.7-29.0%) for susceptibility to TB that is shared across ancestries, highlighting an important host genetic influence on disease. We identified one global host genetic correlate for TB at genome-wide significance (p<5 × 10^-8) in the human leukocyte antigen (HLA)-II region (rs28383206, p-value=5.2 × 10^-9) but failed to replicate variants previously associated with TB susceptibility. These data demonstrate the complex shared genetic architecture of susceptibility to TB and the importance of large-scale GWAS analysis across multiple ancestries experiencing different levels of infection pressure.

SUBMITTER: Schurz H 

PROVIDER: S-EPMC10789494 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature