Common Variants Show Predicted Polygenic Effects on Height in the Tails of the Distribution, Except in Extremely Short Individuals
Figure 3
Comparison of the observed versus simulated mean WAS with models incorporating additional variants.
The plot shows the result of comparing the mean WAS of the short and tall individuals observed from both the HUNT and FINRISK cohorts against that obtained from simulation with different scenarios of additional variants. All rows use the approximate 1.5% tails of the height distribution as extremes, resulting in 566 short and 648 tall individuals. The 1st row shows the result where the model has no additional variants affecting height and thus is identical to that from the 2nd row of Figure 2. The 2nd row shows a model where there are 180 additional common variants that slightly decreases height (allele frequency = 0.3 and effect size (β) = −0.05). This model does not result in any significant change to the simulated WAS of the short individuals and the observed WAS is still significantly different (p = 0.00756). The 3rd row shows a model where there is 1 additional low frequency variant with a large height decreasing effect (allele frequency = 0.005 and effect size (β) = −4). This model results in a large shift in the simulated WAS of the short individuals to the right. The observed WAS is still significantly different (p = 4.54×10−8) than the simulation but in the opposite direction and thus is not consistent with our data. The 4th row shows a model where there is 1 additional low frequency variant that decreases height significantly (allele frequency = 0.005 and effect size (β) = −2). This model results in a shift in the simulated WAS of the short individuals to the right such that the observed WAS is no longer different from the simulation (p = 0.544). The 5th row shows a model where there are 10 additional low frequency variants that moderately decreases height (allele frequency = 0.005 and effect size (β) = −1). This model also results in a shift in the simulated WAS of the short individuals to the right such that the observed WAS is no longer different from the simulation (p = 0.39). The final two models are consistent with our observed data.