An MR method that explores the separate and joint causal effects of two (or potentially more) risk factors on an outcome and is analogous to factorial randomized controlled trial (RCT) designs. Participants in a factorial MR study are categorised into different levels of each risk factor based on their genetic IVs. Where the genetic IV involves multiple SNPs, categories of high vs. low exposure might be defined by being above and below the median of a polygenic risk score (PRS) of those SNPs. For a genetic IV that includes a SNP, the categorisation will be one group of homozygotes versus a group of the heterozygotes and other homozygotes together, or three groups of homozygotes for one allele, heterozygotes, and homozygotes for the other allele. Regression analyses are then conducted with the genetic IV categories.
Genetic IVs for the two (or potentially more) risk factors are the categories defined by genetic variants. These categories need to fulfil the key IV assumptions. Factorial MR may have limited statistical power (in comparison to factorial RCTs and MR of single risk factors).
- Ference BA, Majeed F, Penumetcha R, Flack JM, Brook RD. Effect of naturally random allocation to lower low-density lipoprotein cholesterol on the risk of coronary heart disease mediated by polymorphisms in NPC1L1, HMGCR, or both: a 2 x 2 factorial Mendelian randomization study. J Am Coll Cardiol 2015;65:1552-61.
Other terms in 'Definition of MR and study designs':
- Bidirectional MR
- Binary exposure MR
- Instrumental variable (IV)
- Mendelian randomization (MR)
- Multivariable MR
- One-sample MR
- Two-sample MR
- Two-sample MR with individual participant data (IPD)
- Two-sample MR with summary (aggregate) data
- Two-step/Mediation MR