We also add a post filtering step, to mitigate issues with LD-contamination. Based on consistency with PrediXcan and interpretability of results, we have chosen to use COLOC for filtering. COLOC has the limitation of assuming a single causal variant, and has reduced power in the presence of multiple causal variants. However, colocalization estimation is an active area of research and improved versions or methods will be adopted in the future. We find that BSLMM-based TWAS results have a larger proportion of non-colocalized genes as estimated by COLOC. This could be due to the single variant assumption in COLOC but we believe this is rather a consequence of the polygenic component of BSLMM predictors. Given the predominantly sparse architecture of gene expression traits27, we believe that adding a polygenic component unnecessarily increases the exposure to LD-contamination.
