Tuberculosis severity associates with variants and eQTLs related to vascular biology and infection-induced inflammation

Tuberculosis (TB) remains a major public health problem globally, even compared to COVID-19. Genome-wide studies have failed to discover genes that explain a large proportion of genetic risk for adult pulmonary TB, and even fewer have examined genetic factors underlying TB severity, an intermediate trait impacting disease experience, quality of life, and risk of mortality. No prior severity analyses used a genome-wide approach. As part of our ongoing household contact study in Kampala, Uganda, we conducted a genome-wide association study (GWAS) of TB severity measured by TBScore, in two independent cohorts of culture-confirmed adult TB cases (n = 149 and n = 179). We identified 3 SNPs (P