Serum protein and RNA markers | ||||||||
---|---|---|---|---|---|---|---|---|
Serum IL-6 | Serum sIL-6R | IL-6R 217489_s_at | IL-6ST 234967_at | |||||
End point | AMBITION | RADIATE | Pooled DMARD-IR | AMBITION | RADIATE | Pooled DMARD-IR | RADIATE | RADIATE |
DAS28 | ||||||||
N | 480 | 322 | 2286 | 577 | 423 | 2620 | 217 | 217 |
β | 0.209 | 0.257 | 0.201 | –0.007 | 0.075 | 0.054 | 0.109 | –0.04 |
r2 | 0.051 | 0.072 | 0.044 | 0 | 0.006 | 0.003 | 0.013 | 0.002 |
p | <0.0001 | <0.0001 | <0.0001 | 0.8478 | 0.1018 | 0.0044 | 0.09 | 0.54 |
TJC | ||||||||
N | 481 | 327 | 2305 | 580 | 428 | 2642 | 217 | 217 |
β | –0.186 | 1.455 | 0.138 | –0.154 | 1.28 | 0.054 | 0.27 | 1.276 |
r2 | 0 | 0.009 | 0 | 0 | 0.007 | 0 | 0 | 0.007 |
p | 0.7742 | 0.0938 | 0.6611 | 0.7967 | 0.0889 | 0.8558 | 0.79 | 0.2140 |
SJC | ||||||||
N | 481 | 327 | 2305 | 580 | 428 | 2642 | 217 | 217 |
β | 0.247 | 1.421 | 0.813 | –0.679 | –0.069 | 0.52 | –0.864 | 0.218 |
r2 | 0 | 0.018 | 0.006 | 0.004 | 0 | 0.002 | 0.008 | 0 |
p | 0.6279 | 0.0158 | 0.0003 | 0.1424 | 0.8938 | 0.013 | 0.1950 | 0.7440 |
ESR | ||||||||
N | 481 | 327 | 2299 | 580 | 428 | 2635 | 217 | 217 |
β | 0.19 | 0.172 | 0.151 | 0.039 | –0.003 | 0.023 | 0.164 | –0.132 |
r2 | 0.088 | 0.091 | 0.055 | 0.004 | 0 | 0.001 | 0.082 | 0.053 |
p | <0.0001 | <0.0001 | <0.0001 | 0.132 | 0.9158 | 0.0672 | <0.0001 | 0.0007 |
CRP | ||||||||
N | 481 | 327 | 2305 | 580 | 428 | 2642 | 217 | 217 |
β | 0.363 | 0.429 | 0.35 | 0.007 | 0.019 | 0.019 | 0.228 | –0.145 |
r2 | 0.288 | 0.358 | 0.309 | 0 | 0.001 | 0.001 | 0.089 | 0.036 |
p | <0.0001 | <0.0001 | <0.0001 | 0.8103 | 0.5935 | 0.1242 | <0.0001 | 0.005 |
HAQ | ||||||||
N | 480 | 324 | 2165 | 579 | 425 | 2465 | 217 | 217 |
β | 0.085 | 0.145 | 0.084 | 0.002 | 0.074 | 0.024 | 0.048 | –0.103 |
r2 | 0.019 | 0.062 | 0.018 | 0 | 0.016 | 0.002 | 0.007 | 0.031 |
p | 0.0022 | <0.0001 | <0.0001 | 0.933 | 0.0089 | 0.0504 | 0.22 | 0.009 |
DNA markers | |||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|
Tiers | Gene | Chr | SNP | Population | MAF | End point | n | β | SE | Raw P | FDR P |
1 | IL-6R | 1 | rs1386821 | White | 0.17 | HAQ | 708 | 0.135 | 0.041 | 0.001 | 0.18 |
All | 0.15 | HAQ | 845 | 0.118 | 0.040 | 0.004 | 0.52 | ||||
3 | TOLLIP | 11 | rs5743899 | All | 0.22 | ESR | 893 | 0.15 | 0.03449 | 1.5E-05 | 0.046 |
RUNX1 | 21 | rs2252585 | All | 0.32 | ESR | 905 | 0.1209 | 0.02884 | 3.0E-05 | 0.046 | |
IL-1RAPL1 | 23 | rs12559028 | All | 0.49 | SJC | 905 | 2.182 | 0.5349 | 4.9E-05 | 0.050 | |
rs5943618 | All | 0.44 | SJC | 905 | 2.27 | 0.5424 | 3.1E-05 | 0.046 | |||
rs4829239 | All | 0.38 | SJC | 905 | 2.321 | 0.5592 | 3.6E-05 | 0.046 | |||
rs5927671 | All | 0.45 | ESR | 897 | 0.1181 | 0.02853 | 3.8E-05 | 0.046 |
All results for serum markers are shown. For RNA, the probe sets within each gene were strongly correlated. One probe set each in IL-6R and IL-6ST is shown. For DNA, only associations with raw p<0.01 (tier 1) and FDR ps<0.05 (tiers 2 and 3) were shown. FDR was calculated within the population (white or all) and within the tier.
β, regression coefficient, representing the difference in the end point corresponding to SD in marker value; Chr, chromosome; CRP, C reactive protein; DAS28, Disease Activity Score using 28 joints; DMARD, disease-modifying antirheumatic drug; ESR, erythrocyte sedimentation rate; HAQ, Health Assessment Questionnaire; IL-6ST, IL-6 signal transducer; IR, inadequate responder; MAF, minor allele frequency; MTX, methotrexate; SJC, swollen joint count; TCZ, tocilizumab; TJC, tender joint count.