We explored how often significant variant-level associations between different variants in the same gene have opposing directions of effect on a phenotype. Among quantitative trait associations with at least five significant non-synonymous variants (MAF < 0.1%) in a particular gene, at least 80% of variants had the same direction of effect (Extended Data Fig. 2b). This is in contrast to disease-associated non-coding variants, which can variably affect the direction of gene expression33.
