Table 2.
CNVs Associated With Neurodevelopmental/Psychosis Phenotypes
| SCZ CNVs | Canonical CNV Coordinates (Size in kb) | Cases (N) | Case CNV Coordinates (Size in kb) | Source | Prevalence (%) | P valuea | ||
|---|---|---|---|---|---|---|---|---|
| TRS (n = 509) | SCZ15 (n = 21094) | Uncorrected | Adjusted for FDR | |||||
| 3q29 Del | chr3:195.72–197.35 (1635) | 1 | chr3:195.8–197.1 (1302) | CMA, CLIA | 0.20 | 0.076 | .324 | .714 |
| 7q11.23 Dup | chr7:72.74–74.14 (1398) | 1 | chr7:72.74–74.14 (1395) | CMA | 0.20 | 0.062 | .276 | .714 |
| 15q11.2 Del | chr15:22.81–23.09 (298) | 3 | Cases 1–3: chr15:22.82–23.09 (263) | CMA, CLIA | 0.59 | 0.45 | .491 | .900 |
| 15q11.2-13.1 Dup | chr15:22.81–28.39 (5585) | 4 | Case 1: chr15:23.72–28.51 (4796) | CMA, CLIA | 0.78 | 0.071 | .000787 | .00866* |
| Cases 2–3: chr15:22.82–28.51 (5691) | CMA, CLIA | |||||||
| Case 4: chr15:22.82–29.57 (6750) | CMA, CLIA | |||||||
| 16p11.2 (distal) Del | chr16:28.82–29.05 (224) | 1 | chr16:28.49–29.05 (558) | CMA, CLIA | 0.20 | 0.052 | .242 | .714 |
| 16p11.2 (proximal) Dup | chr16:29.65–30.20 (550) | 6 | Cases 1–4: chr16:29.66–30.19 (535) | WES, CLIA | 1.18 | 0.30 | .661 | 1.00 |
| Cases 5–6: chr16:29.66–30.19 (535) | CMA, CLIA | |||||||
| 16p13.11 Dup | chr16:15.51–16.29 (782) | 1 | chr16:15.12–16.29 (1162) | CLIA | 0.20 | 0.40b | ||
| 22q11.21 Del | chr22:19.04–21.47 (2429) | 4 | Cases 1–4: chr22:18.92–21.46 (2541) | CMA, CLIA | 0.78 | 0.28 | .0529 | .291 |
| NDD CNVs | ||||||||
| 1q21.1 (proximal TAR region) Dup | chr1:145.39–145.81 (413) | 1 | chr1:145.4–145.8 (412) | WES | ||||
| 15q13.3 Dup | chr15:30.94–32.52 (1,572) | 1 | chr15:31.16–32.44 (1280) | CMA, CLIA | ||||
| 16p12.2 Del | chr16:21.95–22.43 (482) | 1 | chr16:21.95–22.43 (478) | CMA, CLIA | ||||
| Total case count (% of TRS sample, n = 509) | 24 (4.7%) | 4.13 | 1.95c | |||||
Note: SCZ, schizophrenia; kb, kilobase pair; TRS, treatment resistant psychotic symptoms; FDR, false discovery rate; Del, deletion; CMA, chromosomal microarray; CLIA, Clinical Laboratory Improvement Amendment (These CNVs were clinically verified in an independent CLIA certified lab); Dup, duplication; WES, whole exome sequencing.
CNVs overlapping >50% with the canonical coordinates of a known neurodevelopmental/psychiatric CNV loci. All coordinates aligned to hg19. For CNVs called from multiple sources (CMA, WES, and CLIA lab), the shown coordinates are those provided in the CLIA certified lab report. *Statistically significant associations with adjusted P-value < .05.
aStatistical tests are based on the rate of CNVs identified using CMA in this TRS sample (N = 492 with CMA data after QC). Four of the 16p11.2 duplications identified from WES were not included. These rates are different than what is shown in the prevalence column, which considers CNVs called from all sources, and from our entire sample (N = 509).
bThis prevalence reflects both duplications and deletions of 16p13.11 region and thus this CNV is not included in loci-based association tests.
cTotal prevalence of SCZ CNVs counting only those present in this TRS sample. For statistical analysis of cumulative SCZ CNV rate, all 12 SCZ CNV loci shown in supplementary table 2 are counted, including both deletions and duplication of 16p13.11 region, and the final prevalence in SCZ was 2.18% (460/21094; Marshall et al.15).