Figure 2. The Mendelian randomization framework for understanding TWAS.
(A) The standard MR model assumes three assumptions on instrumental variable: (i) it must be associated with the exposure, (ii) it must not be associated with confounders, and (iii) it is associated with the outcome only through the exposure. The blue solid line represents the horizontal pleiotropic effects. (B) Multivariate MR analysis with two exposures as an example. (C) Scheme of the two-stage TWAS analysis. (D) Scheme of maximum likelihood-based TWAS analysis.