Table 2.
Combined analysis of the allele frequencies of Xq28 genetic variants in Caucasian systemic sclerosis patients and unaffected controls from Spain, USA, Germany, The Netherlands and UK
| Locus | rs# | Gene | 1/2 | Subgroup (N) | Genotype, N (%) | MAF (%) | M-H Allele test | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|
|
|
|
||||||||||
| 1/1 | 1/2 | 2/2 | p Value* | pFDR† | OR (95% CI)‡ | ||||||
| ChrX: 152937386 | rs1059702 | IRAK1 | A/G | Controls (n=2530) | 70 (2.77) | 599 (23.68) | 1861 (73.56) | 14.60 | |||
| SSc (n=2890) | 107 (3.70) | 729 (25.22) | 2054 (71.07) | 16.31 | 0.028 | 0.070 | 1.13 (1.01 to 1.26) | ||||
| lcSSc (n=1969) | 67 (3.40) | 476 (24.17) | 1426 (72.42) | 15.49 | 0.298 | 0.429 | 1.07 (0.95 to 1.20) | ||||
| dcSSc (n=921) | 40 (4.34) | 253 (27.47) | 628 (68.19) | 18.08 | 1.65E-03 | 4.12E-03 | 1.27 (1.09 to 1.47) | ||||
| ACA+ (n=1145) | 24 (2.10) | 279 (24.37) | 842 (73.54) | 14.28 | 0.734 | 0.734 | 0.98 (0.84 to 1.13) | ||||
| ATA+ (n=610) | 24 (3.93) | 169 (27.70) | 417 (68.36) | 17.79 | 0.017 | 0.087 | 1.23 (1.04 to 1.46) | ||||
| ChrX: 152957662 | rs3027935 | MECP2 | T/C | Controls (n=2539) | 13 (0.51) | 229 (9.02) | 2297 (90.47) | 5.02 | |||
| SSc (n=3003) | 12 (0.40) | 322 (10.72) | 2669 (88.88) | 5.76 | 0.311 | 0.389 | 1.09 (0.92 to 1.30) | ||||
| lcSSc (n=2056) | 7 (0.34) | 227 (11.04) | 1822 (88.62) | 5.86 | 0.343 | 0.429 | 1.09 (0.91 to 1.32) | ||||
| dcSSc (n=947) | 5 (0.53) | 95 (10.03) | 847 (89.44) | 5.54 | 0.778 | 0.778 | 1.04 (0.81 to 1.32) | ||||
| ACA+ (n=1178) | 1 (0.08) | 134 (11.38) | 1043 (88.54) | 5.77 | 0.469 | 0.596 | 1.08 (0.87 to 1.35) | ||||
| ATA+ (n=625) | 4 (0.64) | 52 (8.32) | 569 (91.04) | 4.80 | 0.348 | 0.435 | 0.87 (0.65 to 1.17) | ||||
| ChrX: 152965174 | rs17435 | MECP2 | T/A | Controls (n=2508) | 99 (3.95) | 744 (29.67) | 1665 (66.39) | 18.78 | |||
| SSc (n=2990) | 170 (5.69) | 952 (31.84) | 1868 (62.47) | 21.61 | 5.36E-04 | 2.68E-03 | 1.19 (1.08 to 1.31) | ||||
| lcSSc (n=2044) | 106 (5.19) | 638 (31.21) | 1300 (63.60) | 20.79 | 0.027 | 0.133 | 1.13 (1.01 to 1.26) | ||||
| dcSSc (n=946) | 64 (6.77) | 314 (33.19) | 568 (60.04) | 23.36 | 1.05E-04 | 5.26E-04 | 1.30 (1.14 to 1.48) | ||||
| ACA+ (n=1176) | 48 (4.08) | 368 (31.29) | 760 (64.63) | 19.73 | 0.459 | 0.596 | 1.05 (0.92 to 1.19) | ||||
| ATA+ (n=626) | 38 (6.07) | 199 (31.79) | 389 (62.14) | 21.96 | 0.035 | 0.088 | 1.18 (1.01 to 1.38) | ||||
| ChrX: 152983236 | rs5987201 | MECP2 | T/C | Controls (n=2449) | 6 (0.24) | 176 (7.19) | 2267 (92.57) | 3.84 | |||
| SSc (n=2985) | 8 (0.27) | 241 (8.07) | 2736 (91.66) | 4.31 | 0.468 | 0.468 | 1.07 (0.88 to 1.31) | ||||
| lcSSc (n=2036) | 6 (0.29) | 162 (7.96) | 1868 (91.75) | 4.27 | 0.728 | 0.728 | 1.04 (0.84 to 1.29) | ||||
| dcSSc (n=949) | 2 (0.21) | 79 (8.32) | 868 (91.46) | 4.37 | 0.641 | 0.778 | 1.06 (0.81 to 1.39) | ||||
| ACA+ (n=1181) | 1 (0.08) | 104 (8.81) | 1076 (91.11) | 4.49 | 0.477 | 0.596 | 1.09 (0.85 to 1.40) | ||||
| ATA+ (n=619) | 2 (0.32) | 40 (6.46) | 577 (93.21) | 3.55 | 0.297 | 0.435 | 0.84 (0.60 to 1.18) | ||||
| ChrX: 153011951 | rs5945175 | MECP2 | C/T | Controls (n=2550) | 3 (0.12) | 157 (6.16) | 2390 (93.73) | 3.20 | |||
| SSc (n=2991) | 7 (0.23) | 242 (8.09) | 2742 (91.68) | 4.28 | 0.063 | 0.104 | 1.22 (0.99 to 1.50) | ||||
| lcSSc (n=2038) | 5 (0.25) | 166 (8.15) | 1867 (91.61) | 4.32 | 0.065 | 0.162 | 1.23 (0.99 to 1.55) | ||||
| dcSSc (n=953) | 2 (0.21) | 76 (7.97) | 875 (91.82) | 4.20 | 0.270 | 0.450 | 1.17 (0.88 to 1.55) | ||||
| ACA+ (n=1167) | 3 (0.26) | 97 (8.31) | 1067 (91.43) | 4.41 | 0.036 | 0.178 | 1.32 (1.02 to 1.71) | ||||
| ATA+ (n=628) | 1 (0.16) | 39 (6.21) | 588 (93.63) | 3.26 | 0.590 | 0.590 | 0.91 (0.64 to 1.30) | ||||
*
All p values have been calculated for the allelic model.
ACA, anticentromere antibodies; ATA antitopoisomerase antibodies; dcSSc, diffuse cutaneous SSc; MAF, minor allele frequency; M-H, Mantel–Haenszel test under fixed effect; lcSSc, limited cutaneous SSc; SSc, systemic sclerosis.
†
Benjamini & Hochberg (1995) step-up FDR control correction.
‡
OR for the minor allele.