Children with Early-Onset Psychosis Have Increased Burden of Rare GRIN2A Variants
Abstract
1. Introduction
2. Materials and Methods
3. Results
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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N (%) | |
---|---|
Natal Sex | |
Female | 13 (38.2) |
Male | 21 (61.8) |
Race | |
African American/African | 6 (17.6) |
Asian or Pacific Islander | 1 (2.9) |
European American/European | 21 (61.8) |
Other | 1 (2.9) |
Declined to answer/unknown | 5 (14.7) |
Ethnicity | |
Hispanic/Latino | 7 (20.6) |
Non-Hispanic/Latino | 20 (58.8) |
Other | 2 (5.9) |
Declined to answer/unknown | 5 (14.7) |
Current age (years) | |
13–18 | 15 (44.1) |
19–25 | 16 (47.1) |
26+ | 3 (8.8) |
Average current age | 20 (SD: 4.4) |
Age of onset of psychotic symptoms (years) | |
<8 | 10 (29.4) |
8–12 | 18 (52.9) |
13–18 | 6 (17.6) |
Average age of onset of psychotic symptoms | 9.6 (SD: 3.1) |
Co-occurring diagnoses | |
Anxiety | 12 (35.3) |
ADHD | 18 (52.9) |
ASD | 9 (26.5) |
Depression | 12 (35.3) |
History of developmental delays | 11 (32.4) |
History of epilepsy or seizures | 11 (32.4) |
Intellectual disability | 5 (14.7) |
Chrom | Bp Start | Bp Stop | Gene Symbol | Number of Markers | p-Value | Number of Markers Tested |
---|---|---|---|---|---|---|
chr1 | 161016735 | 161039760 | ARHGAP30 | 7 | 0.49585008 | 7 |
chr1 | 231297857 | 231357302 | TRIM67 | 4 | 0.63673534 | 2 |
chr16 | 9852375 | 10276611 | GRIN2A | 11 | 0.00367797 | 5 |
chr16 | 30709529 | 30755602 | SRCAP | 11 | 0.04454448 | 8 |
chr17 | 17584786 | 17714767 | RAI1 | 16 | 0.3747328 | 5 |
chr19 | 47222763 | 47250251 | STRN4 | 2 | NA | NA |
chr21 | 45958863 | 45960078 | KRTAP10-1 | 6 | 0.8630309 | 4 |
chr4 | 151185593 | 151936879 | LRBA | 14 | 0.35271382 | 10 |
chr6 | 139561197 | 139613276 | TXLNB | 5 | 0.24115499 | 4 |
chr7 | 150709296 | 150721586 | ATG9B | 11 | 0.10667966 | 8 |
Chrom | POS | REF | Alt | Max Consequence | Carrier Count | Allele Freq | p-Value Fisher | Ref Case Count | Het Case Count | Hom Case Count | Ref Ctrl Count | Het Ctrl Count | Hom Ctrl Count |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
chr16 | 9858054 | T | TCGG | Protein altering variant | 0 | 0.0044 | 1 | 34 | 0 | 0 | 31 | 0 | 0 |
chr16 | 9858055 | T | TG | Frameshift variant | 0 | 0.0045 | 1 | 34 | 0 | 0 | 31 | 0 | 0 |
chr16 | 9858072 | G | C | Stop gained | 0 | 0.0044 | 1 | 34 | 0 | 0 | 31 | 0 | 0 |
chr16 | 9858074 | TTTGG | T | Frameshift variant | 0 | 0.0044 | 1 | 34 | 0 | 0 | 31 | 0 | 0 |
chr16 | 9858079 | T | TAAAAAA | Inframe insertion | 0 | 0.0045 | 1 | 34 | 0 | 0 | 31 | 0 | 0 |
chr16 | 9858173 | G | T | Missense variant | 2 | 0.0168 | 0.25 | 32 | 2 | 0 | 34 | 0 | 0 |
chr16 | 9934641 | G | T | Missense variant | 1 | 0.0042 | 1 | 33 | 1 | 0 | 33 | 0 | 0 |
chr16 | 9934969 | G | A | Splice region variant | 1 | 0.0042 | 1 | 33 | 1 | 0 | 33 | 0 | 0 |
chr16 | 9943800 | G | A | Missense variant | 0 | 0.0042 | 1 | 34 | 0 | 0 | 34 | 0 | 0 |
chr16 | 10031844 | G | C | Missense variant | 2 | 0.0085 | 0.5 | 32 | 2 | 0 | 32 | 0 | 0 |
chr16 | 10032161 | T | C | Missense variant | 1 | 0.0042 | 1 | 33 | 1 | 0 | 34 | 0 | 0 |
ID | Natal Sex | Race | Ethnicity | Age of Onset of Psychotic Symptoms |
---|---|---|---|---|
1 | Male | European American/European | Non-Hispanic | 9 |
2 | Male | European American/European | Non-Hispanic | 12 |
3 | Male | European American/European | Non-Hispanic | 12 |
4 | Female | African American/African | Hispanic | 10 |
5 | Male | European American/European | Hispanic | 9 |
6 | Female | European American/European | Non-Hispanic | 4 |
7 | Male | African American/African | Declined to answer | 13 |
Chrom | POS (GRCh37) | REF | Alt | Amino Acid Change | Het OR Hom | ACMG Interpretation | Categories | Rs Number |
---|---|---|---|---|---|---|---|---|
chr16 | 9858173 | G | T | p.Asn1076Lys | het | Benign | BA1, BS2, BP4, BP6 | rs61758995 |
chr16 | 9858173 | G | T | p.Asn1076Lys | het | Benign | BA1, BS2, BP4, BP6 | rs61758995 |
chr16 | 9934641 | G | T | p.Ala505Glu | het | VUS | PM2, PM1 | |
chr16 | 9934969 | G | A | het | Benign | BA1, BS2, BP4, BP6 | rs7193290 | |
chr16 | 10031844 | G | C | p.Pro327Ala | het | Likely Benign | PM2, BS2, BP4 | rs771168389 |
chr16 | 10031844 | G | C | p.Pro327Ala | het | Likely Benign | PM2, BS2, BP4 | rs771168389 |
chr16 | 10032161 | T | C | p.Lys221Arg | het | Benign | BA1, BS2, BP6 | rs61731464 |
ID | Diagnosis | Co-Occurring Condition(s) | Inheritance | Carrier Parent Phenotype | Other Family History of Neuropsychiatric Disease |
---|---|---|---|---|---|
1 | Early-onset schizophrenia | ASD | Paternal | Anxiety, depression, substance use disorder | None noted |
2 | Early-onset psychosis | OCD | Paternal | None noted | Maternal uncle: schizophrenia |
3 | Early-onset psychosis | Epilepsy, microcephaly | Maternal | ADHD | Brother: seizures Family history of bipolar disorder |
4 | Early-onset psychosis | Adenoidectomy, ADHD combined type, asthma, bipolar II disorder, obesity, type 2 diabetes mellitus | Unknown | Unknown | Mother: ADHD Father: PTSD and substance use Maternal grandmother: depression |
5 | Early-onset psychosis | Paternal | Severe OCD without psychotic symptoms | Maternal family history of bipolar disorder, schizophrenia, and ADHD | |
6 | Early-onset psychosis | ADHD, ASD, Chiari malformation, seizures | Unknown | Unknown | Maternal grandmother: bipolar disorder |
7 | Early-onset psychosis | Depression, PTSD, reactive attachment disorder | Unknown | Unknown | Mother: seizures Father: childhood epilepsy (now outgrown) |
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Hojlo, M.A.; Ghebrelul, M.; Genetti, C.A.; Smith, R.; Rockowitz, S.; Deaso, E.; Beggs, A.H.; Agrawal, P.B.; Glahn, D.C.; Gonzalez-Heydrich, J.; et al. Children with Early-Onset Psychosis Have Increased Burden of Rare GRIN2A Variants. Genes 2023, 14, 779. https://doi.org/10.3390/genes14040779
Hojlo MA, Ghebrelul M, Genetti CA, Smith R, Rockowitz S, Deaso E, Beggs AH, Agrawal PB, Glahn DC, Gonzalez-Heydrich J, et al. Children with Early-Onset Psychosis Have Increased Burden of Rare GRIN2A Variants. Genes. 2023; 14(4):779. https://doi.org/10.3390/genes14040779
Chicago/Turabian StyleHojlo, Margaret A., Merhawi Ghebrelul, Casie A. Genetti, Richard Smith, Shira Rockowitz, Emma Deaso, Alan H. Beggs, Pankaj B. Agrawal, David C. Glahn, Joseph Gonzalez-Heydrich, and et al. 2023. "Children with Early-Onset Psychosis Have Increased Burden of Rare GRIN2A Variants" Genes 14, no. 4: 779. https://doi.org/10.3390/genes14040779
APA StyleHojlo, M. A., Ghebrelul, M., Genetti, C. A., Smith, R., Rockowitz, S., Deaso, E., Beggs, A. H., Agrawal, P. B., Glahn, D. C., Gonzalez-Heydrich, J., & Brownstein, C. A. (2023). Children with Early-Onset Psychosis Have Increased Burden of Rare GRIN2A Variants. Genes, 14(4), 779. https://doi.org/10.3390/genes14040779