Derivation and utility of schizophrenia polygenic risk associated multimodal MRI frontotemporal network

• DOI: 10.1038/s41467-022-32513-8
• Publication Date: 2022-08-22T14:04:27Z
• Authors: Shile Qi; Jing Sui; Godfrey Pearlson; Juan Bustillo; Nora I. Perrone-B...; Peter Kochunov; Jessica A. Turner; Zening Fu; Wei Shao; Rongtao Jiang; Xiao Yang; Jingyu Liu; Yuhui Du; Jiayu Chen; Daoqiang Zhang; Vince D. Calhoun
• Keywords: 0301 basic medicine; Multifactorial Inheritance; Bipolar Disorder; Science; Q; Brain; Magnetic Resonance Imaging; Article; 3. Good health; 03 medical and health sciences; Schizophrenia; Humans; Genetic Predisposition to Disease

AbstractSchizophrenia is a highly heritable psychiatric disorder characterized by widespread functional and structural brain abnormalities. However, previous association studies between MRI and polygenic risk were mostly ROI-based single modality analyses, rather than identifying brain-based multimodal predictive biomarkers. Based on schizophrenia polygenic risk scores (PRS) from healthy white people within the UK Biobank dataset (N = 22,459), we discovered a robust PRS-associated brain pattern with smaller gray matter volume and decreased functional activation in frontotemporal cortex, which distinguished schizophrenia from controls with >83% accuracy, and predicted cognition and symptoms across 4 independent schizophrenia cohorts. Further multi-disease comparisons demonstrated that these identified frontotemporal alterations were most severe in schizophrenia and schizo-affective patients, milder in bipolar disorder, and indistinguishable from controls in autism, depression and attention-deficit hyperactivity disorder. These findings indicate the potential of the identified PRS-associated multimodal frontotemporal network to serve as a trans-diagnostic gene intermediated brain biomarker specific to schizophrenia.