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.

Table 2 Baseline characteristics of the study population

Characteristics	RA group (n = 41)	Control group (n = 41)	P value
Sex, female	33 (80.49)	33 (80.49)	1.000
Age, years	56.20 ± 13.28	52.20 ± 10.33	0.132
BMI, kg/m2	22.41 ± 3.31	22.37 ± 2.92	0.346
Smoking status	5 (12.20)	4 (9.76)	1.000
Disease duration, months	6 (2, 8)	-	-
DAS28-ESR	5.20 ± 1.27	-	-

Data are presented as n (%), mean ± SD, or median (interquartile range).

BMI: Body mass index; DAS28-ESR: Disease Activity Score 28-joint count using erythrocyte sedimentation rate; RA: Rheumatoid arthritis.