Genotype epigenome phenotype integration reveals peripheral immune contributions to type I bipolar disorder

In this study led by Lei Hou, the team integrated 833 ChIP-seq maps across five histone marks in peripheral blood immune cells from 88 type I bipolar disorder patients and 92 controls with whole-genome sequencing and clinical data. The analysis identifies disease-associated and genetically influenced regulatory elements, immune pathways involving calcium signaling and endoplasmic reticulum transport, 39 candidate driver genes, and five epigenomic patient subtypes with distinct clinical features and genetic risk profiles. It also nominates compounds predicted to reverse disease-associated epigenomic signatures, highlighting peripheral immune contributions to type I bipolar disorder pathogenesis.