disease) (Holmes et al., 2014). In an empirical test of this hypothesis, one study found that BMI PRS (discovery N = 108, 912) predicted cardiometabolic traits and outcomes, but not coronary artery disease, in an independent cohort of 34, 538 individuals. Each unit increase in the BMI-PRS corresponded to 1.08 kg/m2 increase in BMI, and was associated with inflammation (e.g., C-Reactive Protein: 12% increase), cardiometabolic traits (e.g., fasting insulin: 8.4% increase) and disorders (e.g., type 2 diabetes, OR = 1.29) suggesting that BMI may cause such outcomes. The use of PRS in the study of clinically relevant psychiatric phenotypes is limited, although some argue that cross-trait PRS predictions may, in some cases, be indicative of MR. Current tests of MR in clinical psychology rely on individual loci, arguing that they are less likely to have pleiotropic effect, or create a noisy instrument (e.g., cannabis initiation loci predicting SCZ (Gage et al., 2017)). However, as better powered GWAS of putative causal factors emerge, one may begin to craft PRS as genetic instruments, that may be used to test the plausibility of causality among phenotypes, as long as the potential of pleiotropic effects remains tractable (from a biological and statistical perspective). Several
