Novel polymorphisms in <i>TICAM2</i> and <i>NOD1</i> associated with tuberculosis progression phenotypes in Ethiopian populations

Background Infection by Mycobacterium tuberculosis ( Mtb ) is a necessary but not sufficient cause for tuberculosis (TB). Although numerous studies suggest human genetic variation may influence TB pathogenesis, there is a conspicuous lack of replication, likely due to imprecise phenotype definition. We aimed to replicate novel findings from a Ugandan cohort in Ethiopian populations. Method We ascertained TB cases and household controls ( n = 292) from three different ethnic groups. Latent Mtb infection was determined using Quantiferon to develop reliable TB progression phenotypes. We sequenced exonic regions of TICAM2 and NOD1 . Result Significant novel associations were observed between two variants in NOD1 and TB: rs751770147 [unadjusted p = 7.28 × 10 −5 ] and chr7:30477156(T), a novel variant, [unadjusted p = 1.04 × 10 −4 ]. Two SNPs in TICAM2 were nominally associated with TB, including rs2288384 [unadjusted p = 0.003]. Haplotype-based association tests supported the SNP-based results. Conclusion We replicated the association of TICAM2 and NOD1 with TB and identified novel genetic associations with TB in Ethiopian populations.