Proteome-wide MR identified five proteins significantly associated with mvFibroPsych, while multi-layer brain QTL analysis prioritized CD40 as a potential target.<h4>Conclusions</h4>This study provides strong evidence for a shared genetic factor underlying fibromyalgia, insomnia, depression, and anxiety, linked to synaptic function, brain structure integrity, and neuroinflammatory pathways. Here, CD40 is linked to insomnia.