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

The heritability of susceptibility to tuberculosis disease (TB) has been
well recognized. Over one-hundred genes have been studied as candidates
for TB susceptibility, and several variants were identified by genome-wide
association studies (GWAS), but few replicates. We established the
International Tuberculosis Host Genetics Consortium (ITHGC) 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 < 5x10-8) in the human leukocyte antigen (HLA)-II
region (rs28383206, p-value = 5.2x10-9). 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 pressures.