Poor functional outcomes were connected with worse cognitive performance in schizophrenia, although it was unclear what role uncommon coding variations played in it. For a study, researchers sought to ascertain if ultrarare-constrained variants (URCVs) in individuals with schizophrenia were related to cognition.
Within-case genetic association analysis of URCVs and present cognition and premorbid cognitive capacity was conducted using linear regression. A multivariable linear regression investigation of the effects of URCVs, the polygenic risk score for schizophrenia, the polygenic risk score for intelligence, and the copy number variations linked with schizophrenia on cognitive capacity was conducted. Exome sequencing data from 802 schizophrenia patients were evaluated for premorbid IQ using the National Adult Reading Test and for present cognition using the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery. The UK’s clinical and voluntary mental health services were used to recruit participants. Those having an intellectual impairment diagnosis or a neurological condition that is known to have an impact on cognition were not included. Information was gathered between 2007 and 2015. Between April 2020 and March 2022, data were examined.
The mean (SD) age at the time of the interview was 43.36 (11.87) years, with 499 (62%) males and 303 (38%) women among the 802 participants. Lower present cognition scores (β = −0.18; SE = 0.07; P=.005) were linked to ultrarare restricted variants (n = 400). Premorbid IQ was linked with URCVs in the univariable analysis (β = −0.12; SE = 0.05; P=.02) and somewhat reduced the connection with present cognition (β= −0.09; SE = 0.05; P=.08). The results of URCVs linked with present cognition independent of premorbid IQ were validated by multivariable analysis, which revealed that assessed genetic variables together accounted for 6.2% of the variation in current cognition and 10.3% of the variance in premorbid IQ (β = −0.10; SE = 0.05; P=.03).
The results of the study implied that URCVs, with partially independent relationships before and after the beginning of the condition, contributed to variation in cognitive performance in schizophrenia. Future research may demonstrate that, despite the minimal impact sizes that were calculated, the effect sizes would increase with improved annotation of pathogenic mutations. Genomic information may help identify people who are particularly at risk for cognitive impairment and who might benefit from early intervention or prevention.
Reference: jamanetwork.com/journals/jamapsychiatry/fullarticle/2795508
