Although genetic factors contribute to tuberculosis (TB) risk, no cross-population causal variants have been identified by genome-wide association studies (GWAS). Here, we utilized low-pass whole genome sequencing (lpWGS) with imputation plus detailed epidemiologic risk factors and single-cell expression quantitative loci (sceQTL) to address prior GWAS limitations. Using 947 pulmonary tuberculosis (PTB) cases and 1807 close contact controls in the Regional Prospective Observational Research in TB (RePORT) study in Brazil, we estimated PTB heritability to be 47.7%. We identified 19 SNPs associated with PTB (P