Integrating Mendelian randomization and enzyme-linked immunosorbent assay validation identifies candidate mediators across the rheumatoid arthritis disease continuum

Table 1 Summary of heterogeneity and horizontal pleiotropy test results for CD40, C-C motif chemokine ligand 28, matrix metalloproteinase-1, and interleukin-18 receptor 1

Exposure	Outcome	Heterogeneity tests		Horizontal pleiotropy test	MR-PRESSO		Steiger directionality (proportion correct)
		Cochran’s Q test (P value, IVW)	Rucker’s Q test (P value, MR-Egger)	MR-Egger intercept (P value)	Distortion test (outliers)	Global test (P value)
CD40	RA	0.101	0.093	0.458	NA	0.163	1.0
CCL28	RA	0.175	0.185	0.276	NA	0.171	1.0
MMP-1	RA	0.380	0.358	0.454	NA	0.404	1.0
IL-18R1	RA	0.889	0.908	0.335	NA	0.828	1.0

CCL28: C-C motif chemokine ligand 28; IL-18R1: Interleukin-18 receptor 1; IVW: Inverse-variance weighted; MMP-1: Matrix metalloproteinase-1; MR: Mendelian randomization; MR-PRESSO: Mendelian randomization Pleiotropy RESidual Sum and Outlier; NA: Not available; RA: Rheumatoid arthritis.