Integrating human endogenous retroviruses into transcriptome-wide association studies highlights novel risk factors for major psychiatric conditions

Human endogenous retroviruses (HERVs) are repetitive elements previously implicated in major psychiatric conditions, but their role in aetiology remains unclear. This study performs specialized transcriptome-wide association studies (TWAS) analyzing HERV expression in 792 post-mortem brain samples. In Europeans, 26 HERV expression signals were associated with psychiatric disorders, with five considered high-confidence risk HERVs (two specific to schizophrenia, one shared between schizophrenia and bipolar disorder, and one specific to major depressive disorder). No robust signatures were identified for autism or ADHD in Europeans, or any psychiatric trait in other ancestries due to limited statistical power. The study highlights extensive HERV expression and regulation in the adult cortex, suggesting a role in complex neuropsychiatric traits.

Rodrigo R. R. Duarte, Oliver Pain, Matthew L. Bendall, Miguel de Mulder Rougvie, Jez L. Marston, Sashika Selvackadunco, Claire Troakes, Szi Kay Leung, Rosemary A. Bamford, Jonathan Mill, Paul F. O’Reilly, Deepak P. Srivastava, Douglas F. Nixon, Timothy R. Powell