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A Common KIF6 Polymorphism Increases Vulnerability to Low-Density Lipoprotein Cholesterol: Two Meta-Analyses and a Meta-Regression Analysis

Figure 4

Epidemiological characteristics of a polymorphism that increases vulnerability to LDL cholesterol.

Panel A: Effect of SNP carrier status on the association between LDL cholesterol and risk of CVD. Panel A shows the effect of a one mmol/L change in LDL cholesterol (LDL-C) on the risk of CVD among SNP carriers and non-carriers. The slope of each line represents the relative risk (RR) of CVD associated with a one mmol/L change in LDL-C. The slope (RR) is greater for carriers of a SNP that increases vulnerability to LDL-C indicating a greater increase in the RR of CVD per unit increase in LDL-C, and a corresponding greater reduction in the RR per unit decrease in LDL-C among SNP carriers as compared to non-carriers. The ratio of the slopes (ratio of RR's) is constant and is a measure of effect modification of SNP carrier status on the association between LDL-C and the risk of CVD. Panel B: Effect of LDL cholesterol on the association between SNP carrier status and risk of CVD. Panel B shows that for a SNP that increases vulnerability to LDL-C, the association between that SNP and the risk of CVD will vary by LDL-C level. At higher LDL-C levels, the SNP will be positively associated with the risk of CVD, at moderate LDL-C levels it will have a null association with CVD, and at lower LDL-C levels the SNP will be inversely associated with the risk of CVD. The overall association between the SNP and the risk of CVD will therefore vary according to the average LDL-C level of the population(s) under study. The ratio of the RR for the association between SNP carrier status and the risk of CVD at any two LDL-C levels is a measure of the effect modification of LDL-C on the association between SNP carrier status and the risk of CVD. NB: It can be seen from the Figure that the ratio of the slopes (RR's) in Panel A is exactly equal to the ratio of RR's in Panel B. This observation demonstrates graphically that the magnitude the effect modification of SNP carrier status on the association between LDL-C and the risk of CVD (Panel A) is exactly equal to the magnitude of the effect modification of LDL-C on the association between SNP carrier status and the risk of CVD (Panel B).

Figure 4

doi: https://doi.org/10.1371/journal.pone.0028834.g004