Shared genetic architecture between schizophrenia and subcortical brain volumes implicates early neurodevelopmental processes and brain development in childhood

Weiqiu Cheng*, Dennis van der Meer, Nadine Parker, Guy Hindley, Kevin S O'Connell, Yunpeng Wang, Alexey A Shadrin, Dag Alnæs, Shahram Bahrami, Aihua Lin, Naz Karadag, Børge Holen, Sara Fernandez-Cabello, Chun-Chieh Fan, Anders M Dale, Srdjan Djurovic, Lars T Westlye, Oleksandr Frei, Olav B Smeland, Ole A Andreassen*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

2 Citations (Web of Science)


Patients with schizophrenia have consistently shown brain volumetric abnormalities, implicating both etiological and pathological processes. However, the genetic relationship between schizophrenia and brain volumetric abnormalities remains poorly understood. Here, we applied novel statistical genetic approaches (MiXeR and conjunctional false discovery rate analysis) to investigate genetic overlap with mixed effect directions using independent genome-wide association studies of schizophrenia (n = 130,644) and brain volumetric phenotypes, including subcortical brain and intracranial volumes (n = 33,735). We found brain volumetric phenotypes share substantial genetic variants (74-96%) with schizophrenia, and observed 107 distinct shared loci with sign consistency in independent samples. Genes mapped by shared loci revealed (1) significant enrichment in neurodevelopmental biological processes, (2) three co-expression clusters with peak expression at the prenatal stage, and (3) genetically imputed thalamic expression of CRHR1 and ARL17A was associated with the thalamic volume as early as in childhood. Together, our findings provide evidence of shared genetic architecture between schizophrenia and brain volumetric phenotypes and suggest that altered early neurodevelopmental processes and brain development in childhood may be involved in schizophrenia development.

Original languageEnglish
Pages (from-to)5167-5176
Number of pages10
JournalMolecular Psychiatry
Early online date13 Sept 2022
Publication statusPublished - 2022

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