Table 3:
Genome-wide CRS Differences in EOP relative to ASD and Unselected Control Cohorts
| Deletions | Duplications | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| ASD Contrast | ASD CRS |
EOP CRS |
OR | 95%CI | p-value | ASD CRS |
EOP CRS |
OR | 95%CI | p-value |
| EOP (N=137) | 0.86 | 1.39 | 1.03 | 1.01-1.06 | 0.33 | 1.88 | 1.63 | 0.98 | 0.96-1.01 | 0.61 |
| EOP without ASD (N=90) | 0.86 | 1.00 | 1.01 | 0.97-1.04 | 0.89 | 1.88 | 1.42 | 0.96 | 0.93-1.00 | 0.48 |
| EOP without ID (N=120) | 0.86 | 0.53 | 0.94 | 0.89-0.99 | 0.42 | 1.88 | 1.63 | 0.98 | 0.95-1.01 | 0.64 |
| EOP without schizophrenia (N=99) | 0.86 | 1.59 | 1.04 | 1.02-1.07 | 0.24 | 1.88 | 1.76 | 0.99 | 0.96-1.02 | 0.78 |
| EOP < 13 years old (N=101) | 0.86 | 1.25 | 1.03 | 1.00-1.06 | 0.56 | 1.88 | 1.34 | 0.95 | 0.92-0.99 | 0.42 |
| Control Contrast | Control CRS |
EOP CRS |
OR | 95%CI | p-value | Control CRS |
EOP CRS |
OR | 95%CI | p-value |
| EOP (N=137) | 0.23 | 1.39 | 1.30 | 1.26-1.35 | 9x10−8 | 0.94 | 1.63 | 1.09 | 1.06-1.12 | 0.02 |
| EOP without ASD (N=90) | 0.23 | 1.00 | 1.24 | 1.19-1.30 | 3x10−4 | 0.94 | 1.42 | 1.07 | 1.04-1.11 | 0.17 |
| EOP without ID (N=120) | 0.23 | 0.53 | 1.19 | 1.12-1.27 | 0.04 | 0.94 | 1.63 | 1.09 | 1.06-1.12 | 0.03 |
| EOP without schizophrenia (N=99) | 0.23 | 1.59 | 1.31 | 1.27-1.36 | 3 × 10−7 | 0.94 | 1.76 | 1.10 | 1.07-1.13 | 0.02 |
| EOP < 13 years old (N=101) | 0.23 | 1.25 | 1.34 | 1.28-1.39 | 4 × 10−7 | 0.94 | 1.34 | 1.06 | 1.03-1.10 | 0.25 |
Legend: Effect of gene dosage on EOP risk. Odds ratios are computed using logistic regressions including the CNV risk score (CRS; sum of 1/LOEUF score) for genes totally encompassed in deletions and duplications as the two main explanatory variables. OR represents the mean risk conferred by a deletion or a duplication including 1 intolerant gene (a LOEUF ≤ 0.35). All models were adjusted for sex. CRS presented in the table are the mean score per samples. Sensitivity analysis involved excluding individuals in the EOP sample: 1) with co-occurring ASD; 2) with co-occurring ID; 3) with a diagnosis of schizophrenia; or 5) with psychosis onset prior to age 13. EOP: early-onset psychosis; ASD: autism spectrum disorder cohort (n=5,540); ID: intellectual disability; Controls: unselected population (n=16,50); LOEUF: Loss-of-function observed/expected upper fraction; OR: Odds ratio; 95%CI: 95% Confidence interval