Host Genetic Factors and Clinical Comorbidities Associated With TB Risk

Methods

• Conducted a hospital-based retrospective case–control study using data from the Taiwan Precision Medicine Initiative (TPMI) — a large-scale national genetic program led by Academia Sinica in collaboration with partner hospitals.

• Data were collected from 58,091 participants (June 2019–Dec 2021) at Taichung Veterans General Hospital (TCVGH), integrating genetic profiles with comprehensive electronic health records and medical claims.

• Genomic DNA was extracted using TIANGEN Biotech commercial kits, and DNA quality was confirmed via NanoDrop 2000 spectrophotometry.

• Genotyping performed with the Taiwan Biobank version 2 (TWBv2) Axiom Genome-Wide Array, covering ~714,000 markers enriched for clinically relevant variants (ClinVar, ACMG, GWAS Catalogue, HGMD).

• Participants:

  • TB group: 390 confirmed TB patients (after excluding non-confirmed or latent TB cases).

  • Control group: 3,909 non-TB individuals matched 1:10 by age and gender.

  • Mean age: ~70 years; 65.9% male.

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Key Findings

• Demographic & Clinical Characteristics

  • TB patients were more likely to smoke and had lower BMI than controls.

  • Common comorbidities in TB patients included COPD, bronchiectasis, diabetes, malignancy, autoimmune disease, and steroid use.

• TB Diagnosis Distribution

  • Among culture-positive cases (75.4%), 69.7% had pulmonary TB, 22.1% extra-pulmonary TB, and 8.2% had both.

• HLA Genetic Associations

  • Higher frequencies of HLA-DRB1*16:02 and HLA-DQB1*05:02 were found in TB patients.

  • HLA-DRB1*16:02 significantly associated with TB infection:

    • Adjusted OR = 1.48 (95% CI: 1.08–2.03; p = 0.014).

    • Remained an independent risk factor: OR = 1.47 (95% CI: 1.04–2.09; p = 0.030).

• Clinical Risk and Protective Factors

  • Risk factors:

    • Bronchiectasis (OR 2.76; p < 0.001)

    • Malignancy (OR 1.46; p = 0.002)

    • Diabetes (OR 1.30; p = 0.050)

    • Smoking (OR 1.42; p = 0.012)

    • Steroid use (OR 1.66; p < 0.001)

  • Protective factor:

    • Higher BMI (OR 0.87; p < 0.001)

• Gene–Environment Interaction

• Interaction analysis (adjusted for age, sex, BMI) revealed:

• No added TB risk from HLA-DRB1*16:02 among smokers.

• Significantly increased TB risk in non-smokers carrying HLA-DRB1*16:02 (OR 1.58; 95% CI: 1.02–2.46; p = 0.042).

Source: Lin, S.P., Chen, I.C., Lin, C.H., Hsiao, T.H., Liu, P.Y. and Chen, Y.M., 2025. Host Genetic Factors and Clinical Comorbidities Associated With Tuberculosis Risk. HLA, 106(3), p.e70384.