Table 3B.
SCZ case characteristics across cluster groups in genotyped subsample
| Feature | Cluster 1 (medium EDU) |
Cluster 2 (low EDU) |
Cluster 3 (high EDU) |
Cluster 4 (ID) |
P | |
|---|---|---|---|---|---|---|
| N (%) | 2,109 (57.4%) | 1,064 (29.0%) | 266 (7.2%) | 235 (6.4%) | - | |
| Clustering input variables | Age at first SCZ diagnosis, mean (SD) | 0.07 (0.91) | −0.21 (0.93) | 0.23 (0.93) | −0.14 (0.91) | 1.08×10−18 |
| ID, N (%) | 0 (0%) | 0 (0%) | 0 (0%) | 235 (100%) | - | |
| EDU, mean (SD) | 0.32 (0.31) | −0.98 (0.35) | 2.29 (0.26) | −0.62 (0.73) | <1×10−300 | |
| Parental EDU, mean (SD) | 0.07 (1.01) | −0.21 (0.86) | 0.66 (1.22) | −0.34 (0.84) | 1.27×10−44 | |
| Number of BIP contacts, mean (SD) | 0.00 (0.93) | −0.06 (0.93) | 0.18 (1.53) | −0.002 (0.97) | 0.007 | |
| Birth Year, mean (SD) | 1958 (9.41) | 1957 (10.45) | 1957 (9.99) | 1958 (11.17) | 1.86×10−4 | |
| Male, N (%) | 1,336 (63.3%) | 701 (65.9%) | 141 (53.0%) | 139 (59.1%) | 7.77×10−4 | |
| N with available data on all genetic profiles (%) | 1,814 (57.3%) | 913 (28.9%) | 234 (7.4%) | 203 (6.4%) | - | |
| PRS, mean (SD) | SCZ | 0.01 (1.00) | 0.01 (1.01) | −0.10 (0.96) | −0.01 (1.02) | 0.44 |
| EDU | 0.06 (1.00) | −0.19 (0.96) | 0.44 (0.92) | −0.19 (1.00) | 2.25×10−20 ‡ | |
| IQ | 0.03 (0.99) | −0.09 (0.99) | 0.34 (1.01) | −0.21 (1.00) | 6.70×10−10 ‡ | |
| BIP | 0.03 (1.01) | −0.03 (0.96) | −0.07 (1.06) | −0.04 (0.97) | 0.33 | |
| CNV deletions, mean (SD) | Size of CNVs | −0.01 (0.96) | −0.03 (0.87) | −0.08 (0.58) | 0.31 (1.86) | 7.81×10−5 ‡ |
| Number of CNVs | 0.00 (1.01) | −0.03 (0.96) | −0.01 (1.04) | 0.14 (1.06) | 0.18 | |
| Number of known pathogenic CNVs | −0.03 (0.85) | 0.01 (1.01) | −0.11 (0.03) | 0.33 (2.11) | 9.13×10−6 ‡ | |
| Rare exonic burden, mean (SD) | Number of disruptive or damaging ultra-rare variants in constrained genes | −0.01 (1.00) | 0.05 (1.02) | −0.23 (0.86) | 0.18 (1.06) | 8.88×10−5 ‡ |
Abbreviations: SCZ, schizophrenia; BIP, bipolar disorder; EDU, educational attainment; IQ, intelligence quotient; ID, intellectual disability; PRS, polygenic risk score; CNV, copy number variant. Parental EDU is either from mother or from father if only one among them is available; if both mother’s and father’s EDU are available, take the mean. Except for ID, birth year and male sex, all other variables are the standardized residuals of regression models described as below: age at first SCZ diagnosis, EDU, parental EDU and number of BIP contacts are regressed on birth year and sex; PRS were regressed on the first 5 ancestry principle components (PC) and genotyping waves; CNV deletions were regressed on genotyping waves; Rare exonic burdens were regressed on PC1-PC20 estimated from whole exome sequencing and genotyping waves. Statistical comparisons are one-way ANOVA for continuous variables and chi-square test for categorical variables.
Indicates results exceeding Bonferroni-corrected significance threshold (N=14, P < 0.003) for genetic burden tests.