Poster F83, Tuesday, March 27, 8:00-10:00 am, Exhibit Hall C
Polygenic risk and trajectories of cognitive impairment in schizophrenia: associations limited to the “Cognitively Stable”
Sofia Zaidman1, Evan Giangrande2, Daniel Weinberger3, Karen Berman1, Dwight Dickinson1; 1Clinical and Translational Neuroscience Branch, IRP, NIMH, 2University of Virginia, 3Lieber Institute for Brain Development
This study evaluated associations between cognition and schizophrenia genetic risk profile scores (RPS) across three cognitive trajectory subgroups of people with schizophrenia (PWS). 769 PWS provided demographic and clinical information and completed cognitive assessments as part of the NIMH Study of Schizophrenia Genetics. We performed a two-step cluster analysis to identify cognitive subgroups, using “premorbid” (WRAT) and “current” (WAIS) IQ as clustering indicators. Schizophrenia RPS for 453 PWS were calculated at 10 p-value thresholds based on illness-associated genetic variants identified by the multi-national Psychiatric Genetics Consortium. Across RPS thresholds, we used planned hierarchical regression to test the association of RPS with general cognitive ability (“g”) for the derived cognitive subgroups, controlling for age, sex, and population stratification. Based on 1000 runs, a three-cluster solution was the most frequent result, suggesting one subgroup with high scores on both WRAT and IQ (Cognitively Stable), one with low scores on both WRAT and IQ (Pre-Adolescent Impairment), and one with high scores on WRAT and low IQ (Adolescent Decline). Only the Cognitively Stable subgroup showed significant associations between RPS and “g” at six of 10 RPS thresholds (e.g., at RPS_0.5 p=.01; R2=0.034). Despite higher mean RPS, RPS was not significantly associated with “g” in either the Pre-Adolescent Impairment subgroup or Adolescent Decline subgroups. Although cognitive impairment is a core characteristic of schizophrenia, an association of cognition with common genetic risk for the condition was only observed in one schizophrenia subgroup, whose members were less affected cognitively in early life or adolescence.
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