Table 2.
SNPs across the Chlamydia trachomatis genome identified using permutation-based genome-wide association analysis for (A) ocular localization (non-synonymous only) and (B) disease severity
| (A) | |||||||||||||||
| SNP position | Ocular allele (%) | Urogenital allele (%) | Name A/HAR-13 | CDS | p value | p* | OR | 95% CI (UL) | 95% CI (LL) | t | SE(t) | MAF | N calls at locus | Ocular AA | Urogenital AA |
| 168,413 | A (61.54) | G (93.33) | CTA_0156 | CDS | 5E-05 | 1E-04 | 21.56 | 6.11 | 137.25 | 4.07 | 0.75 | 0.50 | 0.04 | H | R |
| 95,863 | A (60.47) | G (86.67) | CTA_0087 | CDS | 7E-05 | 1E-04 | 9.56 | 3.47 | 33.86 | 3.98 | 0.57 | 0.49 | 0.02 | E | G |
| 785,083 | A (62.20) | G (96.67) | pbpB | CDS | 2E-04 | 1E-04 | 45.92 | 9.34 | 831.41 | 3.70 | 1.03 | 0.49 | 0.05 | I | V |
| 777,345 | A (58.59) | G (96.67) | karG | CDS | 3E-04 | 1E-04 | 40.71 | 8.29 | 736.79 | 3.59 | 1.03 | 0.47 | 0.04 | Y | H |
| 156,982 | C (51.54) | T (90.00) | oppA_1 | CDS | 4E-04 | 1E-04 | 9.44 | 3.13 | 40.92 | 3.54 | 0.63 | 0.43 | 0.02 | V | I |
| 637,206 | A (56.59) | C (96.67) | sctR | CDS | 5E-04 | 1E-04 | 36.25 | 7.39 | 655.80 | 3.48 | 1.03 | 0.45 | 0.03 | K | Q |
| 157,069 | A (51.54) | G (86.67) | oppA_1 | CDS | 7E-04 | 3E-04 | 6.81 | 2.48 | 24.09 | 3.39 | 0.57 | 0.44 | 0.02 | S | P |
| 367,095 | C (60.77) | T (73.33) | CTA_0348 | CDS | 1E-03 | 1E-03 | 4.23 | 1.81 | 10.82 | 3.20 | 0.45 | 0.46 | 0.01 | T | I |
| 544,233 | A (61.54) | G (73.33) | CTA_0510 | CDS | 1E-03 | 3E-04 | 4.23 | 1.81 | 10.82 | 3.20 | 0.45 | 0.46 | 0.02 | R | G |
| 954,865 | A (59.69) | G (73.33) | pmpD | CDS | 2E-03 | 1E-04 | 4.04 | 1.73 | 10.33 | 3.10 | 0.45 | 0.46 | 0.04 | E | G |
| 969,418 | C (59.06) | T (73.33) | sucD | CDS | 2E-03 | 1E-04 | 3.94 | 1.68 | 10.07 | 3.04 | 0.45 | 0.46 | 0.03 | T | I |
| 544,610 | A (61.54) | G (70.00) | atoS | CDS | 3E-03 | 1E-03 | 3.59 | 1.56 | 8.85 | 2.92 | 0.44 | 0.45 | 0.01 | D | G |
| 543,548 | T (60.63) | C (70.00) | CTA_0508 | CDS | 5E-03 | 1E-04 | 0.29 | 0.12 | 0.67 | −2.83 | 0.44 | 0.45 | 0.06 | F | S |
| 969,583 | T (58.73) | C (70.00) | sucD | CDS | 7E-03 | 1E-04 | 0.30 | 0.12 | 0.70 | −2.72 | 0.44 | 0.46 | 0.04 | L | P |
| 44,611 | C (60.63) | T (66.67) | CTA_0043 | CDS | 1E-02 | 1E-04 | 2.96 | 1.30 | 7.10 | 2.53 | 0.43 | 0.45 | 0.04 | A | V |
| 533,906 | T (74.62) | C (50.00) | CTA_0498 | CDS | 1E-02 | 9E-03 | 0.35 | 0.15 | 0.80 | −2.51 | 0.42 | 0.31 | 0.01 | L | P |
| 295,635 | G (61.24) | A (63.33) | CTA_0284 | CDS | 2E-02 | 1E-04 | 0.38 | 0.16 | 0.86 | −2.30 | 0.42 | 0.44 | 0.03 | R | K |
| 95,527 | C (60.77) | T (60.00) | CTA_0087 | CDS | 5E-02 | 4E-02 | 2.24 | 1.00 | 5.15 | 1.94 | 0.41 | 0.44 | 0.01 | S | L |
| 413,567 | A (60.47) | G (60.00) | CTA_0391 | CDS | 6E-02 | 1E-04 | 2.21 | 0.99 | 5.08 | 1.91 | 0.41 | 0.44 | 0.04 | V | A |
| 1,027,490 | G (58.91) | T (60.00) | CTA_0948 | CDS | 7E-02 | 1E-04 | 2.13 | 0.96 | 4.91 | 1.83 | 0.41 | 0.45 | 0.01 | P | Q |
| 777,183 | T (58.59) | C (60.00) | karG | CDS | 7E-02 | 1E-04 | 0.47 | 0.21 | 1.06 | −1.80 | 0.41 | 0.45 | 0.04 | I | V |
| 168,413 | A (61.54) | G (93.33) | CTA_0156 | CDS | 5E-05 | 1E-04 | 21.56 | 6.11 | 137.2 | 4.07 | 0.75 | 0.50 | 0.04 | H | R |
| (B) | |||||||||||||||
| SNP position | Reference allele | Alternative allele | Name A/HAR-13 | CDS/NCR | Strand | p* | p value | t | SE(t) | OR | 95% CI (UL) | (LL) | MAF | N calls at locus | |
| 1,028,728 | C | T | pmpE | CDS | – | 0.013 | 0.011 | −2.550 | 0.555 | 0.078 | 0.026 | 0.232 | 0.310 | 7.042 | |
| 875,804 | C | T | alaS | CDS | – | 0.024 | 0.022 | −2.298 | 0.530 | 0.100 | 0.036 | 0.284 | 0.310 | 4.225 | |
| 939,488 | G | A | glgA | CDS | – | 0.026 | 0.023 | −2.273 | 0.491 | 0.103 | 0.039 | 0.270 | 0.479 | 4.225 | |
| 285,610 | G | A | CTA_0273 | CDS | – | 0.027 | 0.034 | −2.123 | 0.526 | 0.120 | 0.043 | 0.336 | 0.310 | 4.225 | |
| 32,779 | G | A | trmD | CDS | + | 0.032 | 0.031 | −2.160 | 0.525 | 0.115 | 0.041 | 0.323 | 0.310 | 2.817 | |
| 465,330 | C | G | yjfH | CDS | – | 0.037 | 0.042 | −2.032 | 0.519 | 0.131 | 0.047 | 0.362 | 0.310 | 1.408 | |
| 787,841 | A | G | NA | inter | NA | 0.038 | 0.038 | −2.074 | 0.524 | 0.126 | 0.045 | 0.351 | 0.310 | 4.225 | |
| 827,184 | A | G | CTA_0774 | CDS | + | 0.041 | 0.043 | −2.020 | 0.516 | 0.133 | 0.048 | 0.365 | 0.310 | 1.408 | |
| 22,049 | G | T | ileS | CDS | + | 0.057 | 0.050 | −1.962 | 0.505 | 0.141 | 0.052 | 0.378 | 0.324 | 4.225 | |
| 152,011 | G | A | NA | inter | NA | 0.058 | 0.050 | −1.964 | 0.505 | 0.140 | 0.052 | 0.377 | 0.324 | 4.225 | |
| 710,787 | A | C | CTA_0675 | CDS | – | 0.060 | 0.052 | −1.941 | 0.517 | 0.144 | 0.052 | 0.396 | 0.310 | 4.225 | |
| 19,085 | T | C | NA | inter | NA | 0.061 | 0.060 | −1.882 | 0.530 | 0.152 | 0.054 | 0.430 | 0.296 | 5.634 | |
| 388,175 | G | A | CTA_0368 | CDS | – | 0.061 | 0.059 | −1.889 | 0.524 | 0.151 | 0.054 | 0.422 | 0.296 | 1.408 | |
| 696,782 | A | T | rpoD | CDS | – | 0.064 | 0.062 | −1.864 | 0.511 | 0.155 | 0.057 | 0.422 | 0.310 | 1.408 | |
| 286,636 | C | T | lgt | CDS | – | 0.065 | 0.061 | −1.876 | 0.511 | 0.153 | 0.056 | 0.417 | 0.310 | 0.000 | |
| 930,453 | C | T | mutS | CDS | – | 0.067 | 0.061 | −1.876 | 0.511 | 0.153 | 0.056 | 0.417 | 0.310 | 0.000 | |
| 465,525 | C | T | CTA_0439 | CDS | – | 0.067 | 0.062 | −1.865 | 0.472 | 0.155 | 0.061 | 0.391 | 0.493 | 1.408 | |
| 60,858 | G | A | CTA_0057 | CDS | – | 0.068 | 0.070 | −1.813 | 0.512 | 0.163 | 0.060 | 0.445 | 0.310 | 1.408 | |
| 835,039 | G | A | CTA_0782 | CDS | – | 0.070 | 0.061 | −1.876 | 0.511 | 0.153 | 0.056 | 0.417 | 0.310 | 0.000 | |
| 19,005 | A | G | NA | inter | NA | 0.071 | 0.071 | −1.807 | 0.525 | 0.164 | 0.059 | 0.459 | 0.296 | 2.817 | |
| 4554 | A | G | gatB | CDS | + | 0.071 | 0.070 | −1.813 | 0.512 | 0.163 | 0.060 | 0.445 | 0.310 | 1.408 | |
| 303,590 | C | A | murE | CDS | – | 0.072 | 0.061 | −1.876 | 0.511 | 0.153 | 0.056 | 0.417 | 0.310 | 0.000 | |
| 215,130 | C | T | gyrA_1 | CDS | – | 0.072 | 0.062 | −1.864 | 0.511 | 0.155 | 0.057 | 0.422 | 0.310 | 1.408 | |
| 806,382 | C | T | CTA_0761 | CDS | + | 0.073 | 0.058 | −1.896 | 0.530 | 0.150 | 0.053 | 0.424 | 0.296 | 4.225 | |
| 778,783 | G | A | rrf | CDS | – | 0.077 | 0.075 | −1.780 | 0.502 | 0.169 | 0.063 | 0.451 | 0.324 | 2.817 | |
| 136,812 | G | A | incF | CDS | + | 0.079 | 0.075 | −1.780 | 0.502 | 0.169 | 0.063 | 0.451 | 0.324 | 2.817 | |
| 169,573 | G | A | CTA_0156 | CDS | + | 0.082 | 0.077 | −1.771 | 0.523 | 0.170 | 0.061 | 0.474 | 0.310 | 9.859 | |
| 956,953 | C | T | pmpD | CDS | + | 0.082 | 0.072 | −1.800 | 0.523 | 0.165 | 0.059 | 0.461 | 0.296 | 2.817 | |
| 44,990 | A | G | ruvB | CDS | + | 0.087 | 0.086 | −1.718 | 0.493 | 0.179 | 0.068 | 0.472 | 0.338 | 2.817 | |
| 62,140 | G | T | sucA | CDS | + | 0.091 | 0.078 | −1.760 | 0.502 | 0.172 | 0.064 | 0.461 | 0.324 | 5.634 | |
| 542,521 | G | A | CTA_0507 | CDS | – | 0.092 | 0.090 | −1.696 | 0.494 | 0.183 | 0.070 | 0.483 | 0.338 | 2.817 | |
| 181,019 | C | A | CTA_0164 | CDS | – | 0.095 | 0.096 | −1.666 | 0.494 | 0.189 | 0.072 | 0.498 | 0.338 | 4.225 | |
| 151,156 | C | G | CTA_0140 | CDS | – | 0.096 | 0.077 | 1.770 | 0.502 | 5.871 | 2.195 | 15.703 | 0.324 | 4.225 | |
| 1,028,728 | C | A | pmpE | CDS | – | 0.01 | 0.011 | −2.550 | 0.555 | 0.08 | 0.03 | 0.23 | 0.31 | 13.58% | |
| 1,028,728 | C | T | pmpE | CDS | – | 0.0134 | 0.0108 | −2.5504 | 0.5550 | 0.0781 | 0.0263 | 0.2317 | 0.3099 | 7.0423 | |
| 875,804 | C | T | alaS | CDS | – | 0.0242 | 0.0216 | −2.2981 | 0.5295 | 0.1005 | 0.0356 | 0.2836 | 0.3099 | 4.2254 | |
| 939,488 | G | A | glgA | CDS | – | 0.0259 | 0.0230 | −2.2727 | 0.4906 | 0.1030 | 0.0394 | 0.2695 | 0.4789 | 4.2254 | |
| 285,610 | G | A | CTA_0273 | CDS | – | 0.0269 | 0.0338 | −2.1226 | 0.5264 | 0.1197 | 0.0427 | 0.3359 | 0.3099 | 4.2254 | |
| 32,779 | G | A | trmD | CDS | + | 0.0318 | 0.0308 | −2.1596 | 0.5248 | 0.1154 | 0.0412 | 0.3227 | 0.3099 | 2.8169 | |
| 465,330 | C | G | yjfH | CDS | – | 0.0370 | 0.0422 | −2.0315 | 0.5187 | 0.1311 | 0.0474 | 0.3625 | 0.3099 | 1.4085 | |
| 787,841 | A | G | NA | inter | NA | 0.0377 | 0.0381 | −2.0742 | 0.5236 | 0.1257 | 0.0450 | 0.3506 | 0.3099 | 4.2254 | |
| 827,184 | A | G | CTA_0774 | CDS | + | 0.0413 | 0.0433 | −2.0203 | 0.5164 | 0.1326 | 0.0482 | 0.3648 | 0.3099 | 1.4085 | |
| 22,049 | G | T | ileS | CDS | + | 0.0568 | 0.0497 | −1.9624 | 0.5052 | 0.1405 | 0.0522 | 0.3782 | 0.3239 | 4.2254 | |
| 152,011 | G | A | NA | inter | NA | 0.0578 | 0.0495 | −1.9642 | 0.5051 | 0.1403 | 0.0521 | 0.3775 | 0.3239 | 4.2254 | |
| 710,787 | A | C | CTA_0675 | CDS | – | 0.0605 | 0.0523 | −1.9409 | 0.5174 | 0.1436 | 0.0521 | 0.3958 | 0.3099 | 4.2254 | |
| 19,085 | T | C | NA | inter | NA | 0.0608 | 0.0598 | −1.8819 | 0.5298 | 0.1523 | 0.0539 | 0.4302 | 0.2958 | 5.6338 | |
| 388,175 | G | A | CTA_0368 | CDS | – | 0.0610 | 0.0589 | −1.8889 | 0.5238 | 0.1512 | 0.0542 | 0.4222 | 0.2958 | 1.4085 | |
| 696,782 | A | T | rpoD | CDS | – | 0.0638 | 0.0623 | −1.8643 | 0.5114 | 0.1550 | 0.0569 | 0.4223 | 0.3099 | 1.4085 | |
| 286,636 | C | T | lgt | CDS | – | 0.0654 | 0.0606 | −1.8764 | 0.5113 | 0.1531 | 0.0562 | 0.4172 | 0.3099 | 0.0000 | |
| 930,453 | C | T | mutS | CDS | – | 0.0668 | 0.0606 | −1.8764 | 0.5113 | 0.1531 | 0.0562 | 0.4172 | 0.3099 | 0.0000 | |
| 465,525 | C | T | CTA_0439 | CDS | – | 0.0670 | 0.0622 | −1.8650 | 0.4719 | 0.1549 | 0.0614 | 0.3905 | 0.4930 | 1.4085 | |
| 60,858 | G | A | CTA_0057 | CDS | – | 0.0684 | 0.0698 | −1.8134 | 0.5121 | 0.1631 | 0.0598 | 0.4450 | 0.3099 | 1.4085 | |
| 835,039 | G | A | CTA_0782 | CDS | – | 0.0700 | 0.0606 | −1.8764 | 0.5113 | 0.1531 | 0.0562 | 0.4172 | 0.3099 | 0.0000 | |
| 19,005 | A | G | NA | inter | NA | 0.0710 | 0.0707 | −1.8074 | 0.5254 | 0.1641 | 0.0586 | 0.4595 | 0.2958 | 2.8169 | |
| 4554 | A | G | gatB | CDS | + | 0.0713 | 0.0698 | −1.8134 | 0.5121 | 0.1631 | 0.0598 | 0.4450 | 0.3099 | 1.4085 | |
| 303,590 | C | A | murE | CDS | – | 0.0718 | 0.0606 | −1.8764 | 0.5113 | 0.1531 | 0.0562 | 0.4172 | 0.3099 | 0.0000 | |
| 215,130 | C | T | gyrA_1 | CDS | – | 0.0722 | 0.0623 | −1.8643 | 0.5114 | 0.1550 | 0.0569 | 0.4223 | 0.3099 | 1.4085 | |
| 806,382 | C | T | CTA_0761 | CDS | + | 0.0726 | 0.0580 | −1.8960 | 0.5297 | 0.1502 | 0.0532 | 0.4241 | 0.2958 | 4.2254 | |
| 778,783 | G | A | rrf | CDS | – | 0.0767 | 0.0751 | −1.7797 | 0.5021 | 0.1687 | 0.0630 | 0.4514 | 0.3239 | 2.8169 | |
| 136,812 | G | A | incF | CDS | + | 0.0792 | 0.0751 | −1.7797 | 0.5021 | 0.1687 | 0.0630 | 0.4514 | 0.3239 | 2.8169 | |
| 169,573 | G | A | CTA_0156 | CDS | + | 0.0821 | 0.0765 | −1.7712 | 0.5227 | 0.1701 | 0.0611 | 0.4740 | 0.3099 | 9.8592 | |
| 956,953 | C | T | pmpD | CDS | + | 0.0823 | 0.0719 | −1.7998 | 0.5226 | 0.1653 | 0.0594 | 0.4605 | 0.2958 | 2.8169 | |
| 44,990 | A | G | ruvB | CDS | + | 0.0871 | 0.0858 | −1.7181 | 0.4932 | 0.1794 | 0.0682 | 0.4717 | 0.3380 | 2.8169 | |
| 62,140 | G | T | sucA | CDS | + | 0.0914 | 0.0784 | −1.7601 | 0.5024 | 0.1720 | 0.0643 | 0.4605 | 0.3239 | 5.6338 | |
| 542,521 | G | A | CTA_0507 | CDS | – | 0.0916 | 0.0899 | −1.6960 | 0.4940 | 0.1834 | 0.0696 | 0.4830 | 0.3380 | 2.8169 | |
| 181,019 | C | A | CTA_0164 | CDS | – | 0.0953 | 0.0958 | −1.6656 | 0.4940 | 0.1891 | 0.0718 | 0.4979 | 0.3380 | 4.2254 | |
| 151,156 | C | G | CTA_0140 | CDS | – | 0.0955 | 0.0767 | 1.7701 | 0.5019 | 5.8714 | 2.1953 | 15.7035 | 0.3239 | 4.2254 | |
(a) Ocular localization-associated non-synonymous SNPs (p value < 0.1). Position of the SNPs and name of the impacted gene are from the Ct A/HAR-13 (GenBank accession number NC_007429) genome. ‘Allele percentage’ is the percentage of each group where the given allele was present. ‘CDS/NCR’ identifies whether the SNP was in a coding or non-coding region. ‘p*’ indicates p values from 100,024 simulations indicating genome-wide significance at p* < 0.05. ‘t’ is the t statistic; SE(t) is the standard error of the t statistic. ‘OR’ is the adjusted odds ratio (derived from the t statistic). ‘95% CI’ = 95% confidence interval of the OR.; ‘UL’ upper limit, ‘LL’ lower limit. ‘MAF’ is the minor allele frequency. ‘N calls at locus’ is the proportion of isolates which had no base called. ‘AA’ is the amino acid coded for
(b) Disease severity-associated SNPs (p value < 0.1). Disease severity is defined by a composite in vivo conjunctival phenotype derived using principal component analysis using ocular C. trachomatis load and conjunctival inflammatory (P) score (using the modified FPC (follicles, papillary hypertrophy, conjunctival scarring) trachoma grading system [39]). ‘Reference allele’ indicates the reference allele on Ct A/HAR-13 (GenBank accession number NC_007429). ‘CDS/NCR’ identifies whether the SNP was in a coding, non-coding or intergenic region. ‘p*’ = permuted p value after 100,024 simulations indicating genome-wide significance at p* < 0.05. ‘t’ is the t statistic; SE(t) is the standard error of the t statistic. ‘OR’ is the adjusted odds ratio (derived from the t statistic). ‘95% CI’ = 95% confidence interval of the OR; ‘UL’ upper limit, ‘LL’ lower limit. ‘MAF’ is the minor allele frequency. ‘N calls at locus’ is the proportion of isolates which had no base called