Fig. 4: Illustration of pleiotropic effect ratio \(\frac{{\upbeta}_{\mathrm{AL}}}{{\upbeta}_{\mathrm{CC}}}\) and effects toward emmetropic and myopic states.
The figure illustrates genetic effects of AL (βAL) might or might not compensate genetic effects of corneal curvature (βCC) toward myopia or hyperopia. Longer CC (shown by positive βCC; arrow upward) tends to make the eye hyperopic (dashed line in blue) and longer AL (positive βCC; arrow downward) tends to make the eye more myopic (dashed line in red). Similarly, steeper CC (negative βCC, arrow downward) tends to make the eye more myopic and shorter AL (negative βCC; arrow downward) tends to make the eye less myopic. The compensatory pleiotropic effects βAL could offset βCC on myopia or hyperopia at the pleiotropic ratio \(\frac{{\upbeta}_{{\mathrm{AL}}}}{{\upbeta}_{{\mathrm{CC}}}}\) ~ 3, as shown in group A. The compensatory pleiotropic effects βAL, however, cannot offset βCC on myopia or hyperopia at smaller pleiotropic ratio \(\frac{{\upbeta}_{{\mathrm{AL}}}}{{\upbeta}_{{\mathrm{CC}}}}\), as shown in group B. There might be other pleiotropic effect in Group C, besides AL, to compensate genetic effect of CC on myopia. Het-I2, for heterogeneous effects between the variants. All P-value for heterogeneity was >0.05. Pleiotropic effect ratio was calculated at each variant and combined to estimate \(\frac{{\upbeta}_{{\mathrm{AL}}}}{{\upbeta}_{{\mathrm{CC}}}}\) and heterogeneity using the meta-analysis approach (see Methods). Grouping of A, B, and C was the same as in Fig. 3.
