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124. Developmental Neurogenetics of Cortical Thickness and Cortical Surface Area in Schizophrenia: A Multiplex Extended Pedigree Study
Schizophrenia genetic effects on neurodevelopment may remain stable from childhood (as proposed by early neurodevelopmental models) or increase during adulthood, closer to the peak age-of-onset (as proposed by late neurodevelopmental models). To examine whether the genetic correlation between schizophrenia and brain morphology changes across peak age-of-onset, 230 relatives from 32 multiplex, extended pedigrees and 276 unrelated controls underwent MRI scanning and were stratified based on their ages relative to schizophrenia age-of-onset, which peaks at approximately 23 years and plateaus at 42 years (age groups: 12-22, 23-42, 43-84). Genetic analyses revealed that the genetic correlation between schizophrenia and total cortical surface area was high before peak age-of-onset (Rg=-0.839), decreased (p=.002) after peak age-of-onset (Rg=-0.636), and further declined during plateau age-of-onset (Rg=-0.354). However, the genetic correlation between schizophrenia and mean cortical thickness was low before peak age-of-onset (Rg=0.108), increased (p<.001) after peak age-of-onset (Rg=-0.360), then declined afterwards (Rg=-0.092). Overall, schizophrenia genetic effects influence cortical surface area more before peak age-of-onset and cortical thickness after peak age-of-onset. Our findings suggest that the effects of schizophrenia genetic risk influence different aspects of brain structure before and after schizophrenia age-of-onset, emphasizing the importance of examining whether schizophrenia genetic risk variants change expression similarly across neurodevelopment.