Table 1.
CNVs in gene regions previously implicated in ASDs
| Gene/region | Region of significance | Type | Validation | ACC case |
ACC control |
AGRE case |
AGRE control |
Inh | Combined P value |
Permuted P value |
|---|---|---|---|---|---|---|---|---|---|---|
| UBE3A 15q11–13 | chr15: 21200234–26208861 | Dup | MLPA, qPCR | 8 | 0 | 7 (5) | 0 | 6:0:2 (75%) | 1 × 10−5 | <0.001 |
| NRXN1 | chr2: 51120644–51147600 | Del | qPCR | 4 | 0 | 6 (4) | 0 | 4:3:0 (100%) | 4.7 × 10−4 | 0.002 |
| CNTN4 | chr3: 1915190–1915922 | Del | qPCR | 3 | 0 | 7 (4) | 0 | 5:3:0 (100%) | 4.7 × 10−4 | 0.004 |
| 22q11.21 | chr22: 19351264–19358946 | Dup | MLPA | 5 | 0 | 4 | 0 | 2:4:0 (100%) | 0.0010 | 0.008 |
| CNTN4 | chr3: 2548148–2548531 | Dup | qPCR | 1 | 1 | 8 (6) | 0 | 2:3:1 (83%) | 0.0078 | 0.013 |
| 16p11.2 | chr16: 29554844–30085308 | Dup | Affymetrix | 2 | 3 | 7 (3) | 1 | 3:4:1 (88%) | 0.162 | 0.408 |
| 16p11.2 | chr16: 29554844–30085308 | Del | Affymetrix | 3 | 2 | 5 (4) | 2 | 0:0:5 (0%) | 0.246 | 0.300 |
| AUTS2 | chr7: 68576554–68967283 | Dup | Affymetrix | 0 | 0 | 1 | 0 | 1:0:0 (100%) | 0.466 | 0.425 |
| NLGN3 | chrX: 70288980–70460080 | Dup | Affymetrix | 0 | 0 | 1 | 1 | 0:0:0 (NA) | 0.601 | 0.601 |
| SHANK3 | chr22: 49456858–49524956 | Del | Affymetrix | 2 | 1 | 0 | 1 | 4:3:0 (100%) | 1 | 1 |
The number in parenthesis refers to count of unrelated siblings or distinct unrelated families. The sample included 859 ASD cases from the ACC cohort, 1,336 ASD cases from the AGRE cohort, and 2,519 unaffected controls (1,409 ACC discovery controls and 1,110 AGRE replication controls). All CNVs, except 16p11.2, AUTS2, NLGN3 and SHANK3, were experimentally validated in the ACC cohort. Regions listed represent the optimal overlap of cases and significance with respect to controls, as described in the Methods and Supplementary Fig. 5, upper panel. ‘Inh’ column lists the inheritance pattern of each CNV from parents to cases in the format <inherited from mother>:<inherited from father>:<denovo>. Pedigrees provided in Supplementary Fig. 9. The percentage of inheritance is listed in parenthesis next to these three values. Note that parents were not available for all cases.