Table 2.
Significant associations between loci and drug resistance phenotypes identified by locus-based GWAS
| Locus | Known Phenotype Association [13] | Lineage | Observed Phenotype Association | P-value | PhyC |
|---|---|---|---|---|---|
| rpoB | RMP | 2 | XDR, RMP, MDR | 1.9 × 10− 72, 5.2 × 10− 58, 1.4 × 10− 44 | 11 |
| rpoB | RMP | 4 | RMP, MDR, PZA, XDR, EMB | 2 × 10− 94, 1.1 × 10− 35, 1.1 × 10− 33, 2.5 × 10− 30, 6.4 × 10− 23 | 23 |
| rpoB | RMP | 2 + 4 | RMP, MDR, XDR, PZA | 1.6 × 10− 126, 4.1 × 10− 77, 4.1 × 10− 66, 2.1 × 10− 24 | 40 |
| gyrA | FQ | 2 | MOX, FQ, XDR, OFL | 5.2 × 10− 117, 2.5 × 10− 45, 4.3 × 10− 23, 5.1 × 10− 22 | 21 |
| gyrA | FQ | 4 | FQ, CIP, XDR | 4.1 × 10− 38, 5.4 × 10− 36, 6.5 × 10− 27 | 24 |
| gyrA | FQ | 2 + 4 | FQ, OFL, CIP | 1.2 × 10− 63, 1.7 × 10− 32, 2.2 × 10− 26 | 44 |
| pncA | PZA | 2 | XDR | 1.50 × 10− 25 | 0 |
| pncA | PZA | 4 | PZA | 4.50 × 10− 103 | 3 |
| pncA | PZA | 2 + 4 | PZA, EMB, XDR | 5.3 × 10− 101, 1.2 × 10− 29, 6.7 × 10− 22 | 6 |
| embC-embA | EMB | 4 | XDR, EMB | 6.1 × 10− 69, 2.8 × 10− 26 | 8 |
| embC-embA | EMB | 2 + 4 | XDR, EMB | 3.3 × 10− 37, 1.4 × 10− 23 | 13 |
| katG | INH | 2 | INH, MDR | 3.6 × 10−34, 7.3 × 10−24 | 5 |
| katG | INH | 4 | INH | 1.20 × 10−44 | 9 |
| katG | INH | 2 + 4 | INH, MDR | 1.5 × 10−61, 1.5 × 10−36 | 9 |
| embB | EMB | 2 | EMB | 7.20 × 10−27 | 14 |
| embB | EMB | 4 | EMB | 1.80 × 10−56 | 31 |
| embB | EMB | 2 + 4 | EMB | 3.30 × 10−55 | 41 |
| gid | STM | 4 | STM | 7.40 × 10− 55 | 0 |
| gid | STM | 2 + 4 | STM | 1.30 × 10−53 | 0 |
| Rv1313c-Rv1314c | 4 | XDR | 1.40 × 10−54 | 0 | |
| Rv1313c-Rv1314c | 2 + 4 | XDR | 3.30 × 10−32 | 0 | |
| rpsL | STM | 2 | STM | 1.90 × 10−38 | 4 |
| rpsL | STM | 4 | STM | 5.60 × 10−26 | 6 |
| rpsL | STM | 2 + 4 | STM | 6.00 × 10−41 | 13 |
| fadB4-Rv3142c | 4 | XDR | 4.60 × 10−38 | 0 | |
| Rv0526 | 2 + 4 | XDR | 8.70 × 10−37 | 0 | |
| Rv1482c-fabG1 | INH, ETH | 4 | INH | 1.70 × 10−34 | 3 |
| Rv1482c-fabG1 | INH, ETH | 2 + 4 | INH | 3.30 × 10−30 | 14 |
| espE-espF | 2 + 4 | XDR | 5.70 × 10−31 | 0 | |
| tuf | 4 | XDR | 1.50 × 10−29 | 0 | |
| inhA | INH, ETH | 4 | XDR | 2.40 × 10−28 | 0 |
| cut5b-Rv3725 | 4 | XDR | 5.10 × 10−27 | 0 | |
| Rv3007c | 4 | XDR | 7.80 × 10−24 | 0 | |
| Rv2668 | 4 | XDR | 1.30 × 10−23 | 0 | |
| pip-Rv0841 | 2 + 4 | XDR | 8.60 × 10− 23 | 0 | |
| rrs | STM, AG | 2 | KAN | 1.40 × 10−22 | 8 |
| moeX | 4 | XDR | 5.50 × 10− 22 | 0 | |
| lipJ-cinA | 2 + 4 | XDR | 6.20 × 10−22 | 0 | |
| Rv3128c-Rv3129 | 2 | MDR | 7.40 × 10−22 | 0 |
(P-values <1E-21) Novel associations are given in bold. ‘PhyC’ column refers to the number of associations identified through PhyC analysis for the locus and lineage in question. AMK = Amikacin-resistance, AG = Aminoglycoside-resistance, CAP = Capreomycin-resistance, CIP = Ciprofloxacin-resistance, EMB = Ethambutol-resistance, ETH = Ethionamide-resistance, FQ = Fluoroquinolone-resistance, INH = Isoniazid-resistance, KAN = Kanamycin-resistance, MDR = Multidrug-resistant, OFL = Ofloxacin-resistance, PAN = pan-susceptible (no known drug-resistance), PZA = Pyrazinamide-resistance, RMP = Rifampicin-resistance, STM = Streptomycin-resistance, XDR = Extensively drug-resistant