Implementing MR-PRESSO and GCTA-GSMR for pleiotropy assessment in Mendelian randomization studies from a practitioner's perspective

With the advent of very large scale genome-wide association studies (GWASs), the promise of Mendelian randomization (MR) has begun to be fulfilled. However, whilst GWASs have provided essential information on the single nucleotide polymorphisms (SNPs) associated with modifiable risk factors needed for MR, the availability of large numbers of SNP instruments raises issues of how best to use this information and how to deal with potential problems such as pleiotropy. Here we provide commentary on some of the recent advances in the MR analysis, including an overview of the different genetic architectures that are being uncovered for a variety of modifiable risk factors and how users ought to take that into consideration when designing MR studies.