To assess whether a trait with a non-normal distribution (e.g. BMI) or strong marginal associations could cause spurious association between the marginal and variance signals, we recapitulated the analysis pipeline (correlation analysis, enrichment analysis, comparisons of rank Pm and Pv values) in simulations described in the Materials and Methods. Careful assessment of results emanating from these simulations did not reveal evidence of type I error inflation caused by the non-normal distribution of an outcome trait nor strong marginal effects. For instance, we extracted correlation P-values of Pm, Pv and Pint generated from 5,000 simulations. QQ-plots of the 5,000 correlation P-values, 2,500 binomial P-values, and 2,500 Mann-Whitney U test P-values revealed no inflation (S1A–S1C Fig, S2A and S2B Fig and S3A and S3B Fig, respectively). Repeating these analyses on subsets of SNPs with low Pm values did not materially change the results.