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Meta-Analysis
. 2023 Mar 23;14(4):779.
doi: 10.3390/genes14040779.

Children with Early-Onset Psychosis Have Increased Burden of Rare GRIN2A Variants

Margaret A Hojlo  1   2   3   4 , Merhawi Ghebrelul  4   5 , Casie A Genetti  4   5 , Richard Smith  1   2   4   5   6 , Shira Rockowitz  4   5   7 , Emma Deaso  1   3 , Alan H Beggs  4   5   8 , Pankaj B Agrawal  4   5   8   9 , David C Glahn  1   2   3   4   5   10 , Joseph Gonzalez-Heydrich  1   2   3   4   10 , Catherine A Brownstein  1   2   4   5   8
Affiliations
Meta-Analysis

Children with Early-Onset Psychosis Have Increased Burden of Rare GRIN2A Variants

Margaret A Hojlo et al. Genes (Basel). .

Abstract

Background: Children and adolescents with early-onset psychosis (EOP) have more rare genetic variants than individuals with adult-onset forms of the illness, implying that fewer EOP participants are needed for genetic discovery. The Schizophrenia Exome Sequencing Meta-analysis (SCHEMA) study predicted that 10 genes with ultra-rare variation were linked to adult-onset schizophrenia. We hypothesized that rare variants predicted "High" and "Moderate" by the Variant Effect Predictor Algorithm (abbreviated as VEPHMI) in these 10 genes would be enriched in our EOP cohort.

Methods: We compared rare VEPHMI variants in individuals with EOP (N = 34) with race- and sex-matched controls (N = 34) using the sequence kernel association test (SKAT).

Results: GRIN2A variants were significantly increased in the EOP cohort (p = 0.004), with seven individuals (20% of the EOP cohort) carrying a rare VEPHMI variant. The EOP cohort was then compared to three additional control cohorts. GRIN2A variants were significantly increased in the EOP cohort for two of the additional control sets (p = 0.02 and p = 0.02), and trending towards significance for the third (p = 0.06).

Conclusion: Despite a small sample size, GRIN2A VEPHMI variant burden was increased in a cohort of individuals with EOP in comparison to controls. GRIN2A variants have been associated with a range of neuropsychiatric disorders including adult-onset psychotic spectrum disorder and childhood-onset schizophrenia. This study supports the role of GRIN2A in EOP and emphasizes its role in neuropsychiatric disorders.

Keywords: genetics; genomics; psychosis; schizophrenia.

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Conflict of interest statement

Author J.G.H. holds equity in and is founding head of the scientific advisory board for Mightier/Neuromotion Labs, a company making emotional regulation training video games and has received consulting income from Alkermes, Inc., Neurocrine, and Sunovion pharmaceutical companies. A.H.B. has consulted and received compensation or honoraria from F. Hoffman-La Roche AG, GLG Inc., Guidepoint Global, and Kate Therapeutics, and holds equity in Kinea Biosciences and Kate Therapeutics. The remaining authors declare no conflict of interest.

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