Table 3.

Mediation of change in proteins on the association between change in RDW and all-cause mortality (sorted by p-value in indirect association).

	Mediator		Total association of RDW with all-cause mortality				Direct association of RDW with all-cause mortality				Indirect association of RDW with all-cause mortality through mediator				Proportion mediated
Rank	Target	EntrezGene	β	95%CI		p-value	β	95%CI		p-value	β	95%CI		p-value
		Symbol
1	IGFBP-2	IGFBP2	0.22	0.05	0.86	0.03	0.28	0.07	1.12	0.072	0.77	0.6	0.99	0.038	23.5%
2	C7	C7	0.23	0.06	0.94	0.041	0.31	0.08	1.28	0.106	0.75	0.56	0.998	0.048	25.8%

Mediation analysis was performed using SAS macro (%macro mediation for survival data, Valeri & VanderWeele, 2015). Exposure-outcome association was examined by running protein-specific accelerated failure time model with exponential estimation. RDW-mediator (protein) associations were modeled with multivariable linear regression model. All models were adjusted for age, sex, body mass index, smoking status (current smoker or not), education level (6-year education or higher education or not), and haemoglobin. RDW and proteins were measured at baseline. Outcome was 15-year all-cause mortality.