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Table 2 Significant associations between loci and drug resistance phenotypes identified by locus-based GWAS

From: Genome-wide analysis of Mycobacterium tuberculosis polymorphisms reveals lineage-specific associations with drug resistance

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

  1. (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