Fig. 1

Directed acyclic graph (DAG) to highlight the MR framework. The MR assumptions for the instrumental variable (in this case maternal rs1051730) are shown in red: 1 The instrumental variable needs to be associated with the exposure. 2 The instrumental variable is independent of confounding factors that confound the association of the exposure and the outcome. 3 The instrumental variable is independent of the outcome given the exposure and the confounding factors. The MR analysis estimates the effect between the exposure and the outcome shown in blue. The MR analysis is adjusted for offspring sex and ancestry principal components (and genetic batch variables in MoBa). These are summarised in the measured confounder variable Z. U stands for unmeasured confounders, which we are unable to include in the analysis