Table 3.
Adjustment for, and stratification by, anti‐CCP statusa
| Anti‐CCP positive | Anti‐CCP negative | Adjusted for anti‐CCP status | ||||
|---|---|---|---|---|---|---|
| Effect size (95% CI) | P | Effect size (95% CI) | P | Effect size (95% CI) | P | |
| Shared epitope | ||||||
| Larsen score | 1.05 (−1.45, 3.54) | 0.205 | 0.23 (−0.61, 1.07) | 0.295 | 0.16 (−0.80, 1.11) | 0.373 |
| DAS28 | 1.13 (0.85, 1.50) | 0.205 | 1.08 (0.90, 1.28) | 0.206 | 1.10 (0.95, 1.27) | 0.104 |
| FOXO3A (rs12212067) | ||||||
| Larsen score | −1.82 (−4.90, 1.26) | 0.123 | −0.98 (−1.96, 0.01) | 0.026 | −1.26 (−2.49, −0.03) | 0.023 |
| DAS28 | 0.78 (0.60, 1.02) | 0.033 | 0.80 (0.66, 0.96) | 0.010 | 0.78 (0.67, 0.90) | 4.3 × 10−4 |
The association studies presented in Table 1 for the Larsen score in rheumatoid arthritis patients and in Table 2 for the Disease Activity Score in 28 joints (DAS28) in inflammatory polyarthritis patients were again performed either by adjusting for the anti–cyclic citrullinated peptide (anti‐CCP) status; that is, the analysis was restricted to anti‐CCP–positive disease or anti‐CCP–negative disease. Since the effect of the shared epitope is almost completely mediated by anti‐CCP, it disappears completely. However, the adjustment has no major influence on the association of FOXO3A rs12212067. Stratification decreases the sample size and therefore the power, which is likely to explain the lack of significance for the Larsen score in the smaller anti‐CCP–positive group. Overall, these results indicate that the biologic pathways that mediate the effect of the shared epitope and FOXO3A are different. P values are 1‐tailed. See Tables 1 and 2 for explanations of dimensions and interpretation of effect sizes. 95% CI = 95% confidence interval.