Table 1.
The distribution of alleles of 16 SNPs in the extended CTLA-4 gene locus encompassing CD28, CTLA-4 and ICOS in the Norwegian and UK patients and controls cohorts
| DIL107 | AAD G | AAD T | Ctrls G | Ctrls T | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 489 | 129 | 500 | 150 | 0.985 | 1.14 | 0.95 | 0.344 | 48.24 | P=0.52 | P=0.39 | |||
| Norway | 575 | 177 | 591 | 155 | 0.98 | 0.85 | −1.29 | 0.199 | 51.76 | P=0.99 | P=0.57 | P=0.22 | ||
| Meta random | 0.98 | −0.14 | 0.885 | 2.45 | 0.12 | P=0.65 | P=0.06 | |||||||
| rs3181096 | AAD C | AAD T | Ctrls C | Ctrls T | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 412 | 198 | 412 | 218 | 0.965 | 1.1 | 0.8 | 0.424 | 45.6 | P=0.31 | P=0.73 | |||
| Norway | 504 | 236 | 464 | 284 | 0.975 | 1.31 | 2.46 | 0.014 | 54.4 | P=0.054 | P=0.041 | P=0.006 | ||
| Meta random | 1.21 | 2.22 | 0.027 | 1.12 | 0.29 | P=0.03 | P=0.13 | |||||||
| rs1181389 | AAD T | AAD C | Ctrl T | Ctrl C | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 476 | 104 | 583 | 102 | 0.95 | 0.8 | −1.46 | 0.145 | 45.98 | P=0.43 | P=0.46 | |||
| rs1181388 | AAD G | AAD A | Ctrl G | Ctrl A | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 515 | 81 | 551 | 105 | 0.97 | 1.21 | 1.2 | 0.231 | 47.55 | P=0.29 | P=0.15 | |||
| Norway | 636 | 114 | 631 | 103 | 0.975 | 0.91 | −0.64 | 0.525 | 52.45 | P=0.50 | P=0.69 | P=0.52 | ||
| Meta random | 1.04 | 0.3 | 0.767 | 1.72 | 0.19 | P=0.84 | P=0.77 | |||||||
| rs3116507 | AAD A | AAD G | Ctrl A | Ctrl G | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 475 | 141 | 496 | 144 | 0.98 | 0.98 | −0.16 | 0.869 | 45.38 | 0.40 | P=0.57 | |||
| Norway | 565 | 183 | 570 | 164 | 0.975 | 0.89 | −0.96 | 0.335 | 54.62 | 0.54 | P=0.35 | P=0.21 | ||
| Meta random | 0.93 | −0.82 | 0.41 | 0.28 | 0.6 | P=0.92 | P=0.18 | |||||||
| rs11571308 | AAD C | AAD T | Ctrl C | Ctrl T | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| Norway | 646 | 92 | 651 | 87 | 0.97 | 0.94 | −0.4 | 0.69 | 59.04 | P=0.47 | P=1.0 | P=0.90 | ||
| rs5742909 | AAD C | AAD T | Ctrl C | Ctrl T | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 560 | 44 | 588 | 36 | 0.955 | 0.78 | −1.07 | 0.283 | 37.72 | P=0.57 | P=0.11 | |||
| Promoter_1661 | AAD A | AAD G | Ctrl A | Ctrl G | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 486 | 94 | 556 | 94 | 0.956 | 0.87 | −0.85 | 0.396 | 42.94 | 1.00 | P=0.92 | |||
| Norway | 611 | 135 | 598 | 122 | 0.965 | 0.92 | −0.58 | 0.562 | 57.06 | 0.53 | P=0.73 | P=0.61 | ||
| Meta random | 0.9 | −0.99 | 0.32 | 0.07 | 0.79 | P=0.63 | P=0.27 | |||||||
| rs231775 | AAD A | AAD G | Ctrl A | Ctrl G | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 361 | 257 | 400 | 260 | 0.995 | 0.91 | −0.8 | 0.425 | 47.52 | 0.19 | P=0.013 | |||
| Norway | 382 | 370 | 437 | 313 | 0.985 | 0.74 | −2.9 | 0.004 | 52.48 | 0.10 | P=0.003 | P=0.003 | ||
| Meta random | 0.82 | −1.91 | 0.055 | 1.87 | 0.17 | P=0.04 | P=0.27 | |||||||
| rs231726 | AAD C | AAD T | Ctrl C | Ctrl T | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 387 | 211 | 410 | 222 | 0.955 | 0.99 | −0.06 | 0.954 | 48.49 | P=0.67 | P=0.008 | |||
| Norway | 411 | 325 | 467 | 269 | 0.965 | 0.73 | −2.97 | 0.003 | 51.51 | P=0.10 | P=0.002 | P=0.002 | ||
| Meta random | 0.85 | −1.08 | 0.282 | 3.75 | 0.05 | P=0.16 | P=0.40 | |||||||
| rs231727 | AAD G | AAD A | Ctrl G | Ctrl A | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 381 | 207 | 433 | 225 | 0.965 | 0.96 | −0.37 | 0.709 | 47.47 | P=0.41 | P=0.023 | |||
| Norway | 420 | 328 | 457 | 269 | 0.97 | 0.75 | −2.66 | 0.008 | 52.53 | P=0.09 | P=0.007 | P=0.007 | ||
| Meta Random | 0.84 | −1.43 | 0.154 | 2.22 | 0.14 | P=0.10 | P=0.36 | |||||||
| rs231730 | AAD T | AAD A | Ctrl T | Ctrl A | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| Norway | 586 | 150 | 579 | 141 | 0.955 | 0.95 | −0.38 | 0.704 | 56.97 | P=0.35 | P=0.85 | P=0.85 | ||
| rs2882973 | AAD T | AAD C | Ctrl T | Ctrl C | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 401 | 215 | 431 | 225 | 0.985 | 0.97 | −0.23 | 0.821 | 46.53 | P=0.56 | P=0.13 | |||
| Norway | 453 | 301 | 490 | 262 | 0.99 | 0.8 | −2.04 | 0.042 | 53.47 | P=0.20 | P=0.048 | P=0.02 | ||
| Meta random | 0.88 | −1.35 | 0.176 | 1.44 | 0.23 | P=0.18 | P=0.37 | |||||||
| rs3116505 | AAD C | AAD T | Ctrl C | Ctrl T | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 395 | 211 | 411 | 217 | 0.96 | 0.99 | -0.1 | 0.922 | 46.71 | P=0.68 | P=0.10 | |||
| Norway | 428 | 286 | 477 | 259 | 0.95 | 0.81 | -1.91 | 0.056 | 53.29 | P=0.30 | P=0.045 | P=0.03 | ||
| Meta random | 0.89 | -1.19 | 0.235 | 1.47 | 0.23 | P=0.26 | P=0.46 | |||||||
| rs10183087 | AAD A | AAD C | Ctrl A | Ctrl C | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 444 | 158 | 456 | 172 | 0.955 | 1.06 | 0.45 | 0.651 | 50.91 | P=0.89 | P=0.66 | |||
| Norway | 594 | 146 | 595 | 143 | 0.97 | 0.98 | −0.17 | 0.864 | 49.09 | P=0.45 | P=0.39 | P=0.94 | ||
| Meta random | 1.02 | 0.2 | 0.839 | 0.19 | 0.66 | P=0.54 | P=0.83 | |||||||
| rs1896286 | AAD T | AAD G | Ctrl T | Ctrl G | Call rate | OR | Z | P | Q hetero | P hetero | Weight | iAAD | APS II | 21-OH+ N |
| UK | 372 | 238 | 382 | 274 | 0.985 | 1.12 | 1 | 0.319 | 46.82 | P=0.67 | P=0.42 | |||
| Norway | 445 | 275 | 444 | 290 | 0.955 | 1.06 | 0.51 | 0.607 | 53.18 | P=0.38 | P=0.96 | P=0.46 | ||
| Meta random | 1.09 | 1.06 | 0.29 | 0.14 | 0.71 | P=0.35 | P=0.42 |
Abbreviations: AAD, autoimmune Addison’s disease; APS II, autoimmune polyendocrinopathy type II; APS II, P-value for analysis of only APS II; Ctrl, control subjects; OR, odds ratio; Z, Z-value for meta-analysis; P, P-value for the different cohorts and for the meta-analysis using the random model for calculations; Q hetero, Q-value for heterogeneity; P hetero, P-value for heterogeneity; Weight, relative weight using the random model; iAAD, P-value for analysis of only isolated AAD; 21-OH+ N, P-value for analysis of Norwegian patients with positive anti-21-OH autoantibodies.
The distribution of alleles is given in numbers for the cohort of patients with AAD (cases) and for control subjects (Ctrl). The call rates given in the table are the combined call rate for controls and patients. All SNPs with a combined call rate of <95% have been rejected. Analyses have been executed by the program ‘Comprehensive meta-analysis version 2.0’ (www.meta-analysis.com) using a random effects model. P-values which mark a significant association (P<0.05) are marked in bold text. Norwegian cohort: Total AAD cases: N=382 (iAAD N=162; APS II N=220). Total controls: N=380. UK cohort: Total AAD cases: N=309 (iAAD N=135; APS II N=174). Total controls: N=335.