MR Dictionary

Harmonization failure (in two-sample MR)

When one or more genetic IVs have different effect allele between exposure and outcome datasets of summary association results. This is of greater concern for palindromic variants with high minor allele frequency, especially when strand issues are a possibility (Figure 1.1). 

To overcome errors due to harmonization, it is advised to harmonize using automated scripts that have been thoroughly tested (for example, those used in MR-Base) and check the correlation between effect allele frequencies before and after harmonizing. It is also useful to provide pre- and post-harmonization datasets to allow assessment of the quality of the harmonization and perform sensitivity analysis to evaluate the influence of variants difficult to harmonize (e.g., palindromic variants with high minor allele frequency). 


Other terms in 'Sources of bias and limitations in MR':