Host Genetic Factors and Clinical Comorbidities Associated With Tuberculosis Risk.
HLA influence the immune response, shaping genetic susceptibility or resistance to tuberculosis (TB). This study aimed to investigate the associations of host genetics and comorbidities with TB infection in Taiwanese populations. This retrospective case-control study utilised data from the Taiwan Precision Medicine Initiative. TB cases and non-TB controls were compared using genome-wide association studies (GWAS), HLA allele typing, and genotype data. Multivariate logistic regression identified independent predictors of TB and interactions between risk factors. A total of 390 TB cases and 3,909 controls were analysed. Risk factors for TB included bronchiectasis (OR = 2.76; 95% CI 1.54-4.44; p < 0.001), diabetes mellitus (OR = 1.30; 95% CI 1.00-1.68; p = 0.050), malignancy (OR = 1.46; 95% CI 1.15-1.85; p = 0.002), smoking (OR = 1.42; 95% CI 1.08-1.88; p = 0.012), and steroid use (OR = 1.66; 95% CI 1.29-2.13; p < 0.001). HLA-DRB1*16:02 was associated with a higher frequency in the TB group (OR = 1.47; 95% CI 1.04-2.09; p = 0.030). Interaction analysis showed HLA-DRB1*16:02 increased TB risk in non-smokers (OR = 1.58; 95% CI 1.02-2.46; p = 0.042), but not in smokers. HLA-DRB1*16:02 was associated with a higher risk for TB. While carriers of HLA-DRB1*16:02 did not exhibit an increased risk of TB among smokers, we demonstrated a heightened risk among non-smokers.