Human-specific evolutionary markers linked to foetal neurodevelopment modulate brain surface area in schizophrenia

• DOI: 10.1038/s42003-023-05356-2
• Publication Date: 2023-10-13T18:02:13Z
• Authors: Maria Guardiola-R...; Carmen Almodóvar-...; Angelo Arias-Magn...; Mariona Latorre-G...; Sergi Papiol; Erick J. Canales-...; María Ángeles Gar...; Paola Fuentes-Cla...; Josep Salavert; Josep Tristany; Llanos Torres; Elena Rodríguez-Cano; Raymond Salvador; Edith Pomarol-Clotet; Mar Fatjó-Vilas
• Keywords: Human brain

Abstract Schizophrenia may represent a trade-off in the evolution of human-specific ontogenetic mechanisms that guide neurodevelopment. Human Accelerated Regions (HARs) are evolutionary markers functioning as neurodevelopmental transcription enhancers have been associated with brain configuration, neural information processing, and schizophrenia risk. Here, we investigated influence HARs’ polygenic load on neuroanatomical measures through case-control approach (128 patients 115 controls). To this end, calculated global Polygenic Risk Score (Global PRS SZ ) specific to HARs (HARs ). We also estimated burden restricted linked transcriptional regulatory elements active foetal (FB-HARs adult (AB-HARs explored main effects PRSs x diagnosis interactions regional cortical thickness (CT) surface area (SA). The results indicate higher FB-HARs is patients’ lower SA lateral orbitofrontal cortex, superior temporal pars triangularis paracentral lobule. While noHARs-derived show an effect risk, our findings suggest regulation during prenatal period underlies variability, highlighting role these genomic architecture.