New preprint: Genetic risk effects on psychiatric disorders act in sets

I’m very happy to share that our new preprint, “Genetic Risk Effects on Psychiatric Disorders Act in Sets”, is now online on medRxiv, find it here.

This work has been years in the making and brings together a truly collaborative effort. In it, we investigate how genetic risk contributes to five major psychiatric disorders — not just individually (additively), but in coordinated sets. Using both polygenic risk scores (PRS) from large-scale meta-analyses and family-based genetic risk scores (FGRS) from national register data, we apply the Coordinated Epistasis framework previously published by Andy Dahl, Noah Zaitlen et al. in PNAS to better understand the genetic architecture underlying these complex conditions.

Our results suggest that genetic effects within and across psychiatric disorders are more structured than previously appreciated. Rather than acting additively, risk variants operate in distinct sets — a finding that support the existence of unrecognized subtypes and shed light on how we may understand comorbidities. We also find that some shared genetic signals across disorders may reflect broader confounding factors rather than disorder-specific mechanisms.

It’s been incredibly rewarding to see this project come together, and I’m deeply grateful to my co-authors and mentors, especially Na Cai, Andrew Dahl, Andrew Schork, and Jonathan Flint. A special thank you as well to the UK Biobank and iPSYCH participants — without whom this research wouldn’t be possible.