Table 1. Burden analysis for (a) all CNVs; (b) deletions; (c) duplications in independent cases compared with population controls.
| No. of CNVs | Average no. of CNVs per individual | Proportion of sample with one or more CNV | Average total length of CNVs spanned per individual (kb) | Average CNV size (kb) | Average no. of genes spanned by CNVs per individual | Proportion of CNVs containing at least one gene | Average no. of genes per total CNV (kb) | |
|---|---|---|---|---|---|---|---|---|
| Total Burden | ||||||||
| Independent cases and population controls | ||||||||
| Cases | 1432 | 11.28 | 1 | 717.4 | 63.75 | 14.29 | 0.95 | 0.02 |
| Controls | 2693 | 10.01 | 1 | 513.9 | 51.55 | 10.34 | 0.99 | 0.02 |
| Empirical P-value | 0.003 | 1 | 0.0001 | 0.0005 | 0.0007 | 1 | 0.95 | |
| All SLIC family members and population controls | ||||||||
| Family members | 4081 | 10.6 | 720.3 | 70.09 | 12.84 | |||
| Controls | 2693 | 10.01 | 513.9 | 51.55 | 10.34 | |||
| Empirical P-value | 0.03 | 0.0001 | 0.0001 | 0.0005 | ||||
| Affected SLIC family members and population controls | ||||||||
| Family members | 770 | 10.69 | 773.1 | 77.26 | 12.46 | |||
| Controls | 2693 | 10.01 | 513.9 | 51.55 | 10.34 | |||
| Empirical P-value | 0.08 | 0.0001 | 0.0001 | 0.02 | ||||
| Unaffected SLIC family members and population controls | ||||||||
| Family members | 501 | 10.89 | 792.2 | 71.24 | 13.85 | |||
| Controls | 2693 | 10.01 | 513.9 | 51.55 | 10.34 | |||
| Empirical P-value | 0.07 | 0.0002 | 0.0001 | 0.005 | ||||
| Independent cases selected on the basis of low NWR and population controls | ||||||||
| Cases | 674 | 11.42 | 1 | 704 | 60.46 | 12.51 | 0.95 | 0.02 |
| Controls | 2693 | 10.01 | 1 | 513.9 | 51.55 | 10.34 | 0.99 | 0.02 |
| Empirical P-value | 0.004 | 1 | 0.0004 | 0.03 | 0.03 | 1 | 0.92 | |
| Deletions | ||||||||
| Independent cases vs controls | ||||||||
| Cases | 1027 | 8.09 | 1 | 356 | 45.19 | 7.8 | 0.92 | 0.03 |
| Controls | 1878 | 6.98 | 1 | 236.4 | 34.77 | 5.6 | 0.94 | 0.03 |
| Empirical P-value | — | 0.001 | 1 | 0.0001 | 0.0003 | 0.0007 | 0.86 | 0.64 |
| All SLIC family members and population controls | ||||||||
| Family members | 2995 | 7.78 | 344.8 | 45.51 | 7.44 | |||
| Controls | 1878 | 6.98 | 236.4 | 34.77 | 5.6 | |||
| Empirical P-value | — | 0.002 | 0.0001 | 0.0001 | 0.0005 | |||
| Affected SLIC family members and population controls | ||||||||
| Family members | 546 | 7.58 | 352.9 | 49.3 | 6.96 | |||
| Controls | 1878 | 6.98 | 236.4 | 34.77 | 5.6 | |||
| Empirical P-value | 0.07 | 0.0001 | 0.0002 | 0.04 | ||||
| Unaffected SLIC family members and population controls | ||||||||
| Family members | 364 | 7.91 | 376.2 | 46.81 | 8.59 | |||
| Controls | 1878 | 6.98 | 236.4 | 34.77 | 5.6 | |||
| Empirical P-value | 0.03 | 0.0001 | 0.002 | 0.002 | ||||
| Duplications | ||||||||
| Independent cases vs controls | ||||||||
| Cases | 401 | 3.16 | 0.91 | 392.5 | 121.7 | 6.44 | 0.76 | 0.02 |
| Controls | 813 | 3.02 | 0.96 | 286.4 | 89.41 | 4.72 | 0.86 | 0.03 |
| Empirical P-value | — | 0.31 | 0.99 | 0.003 | 0.005 | 0.07 | 1 | 0.97 |
| All SLIC family members and population controls | ||||||||
| Family members | 1072 | 393.3 | 129 | |||||
| Controls | 813 | 286.4 | 89.41 | |||||
| Empirical P-value | — | 0.0004 | 0.0001 | |||||
| Affected SLIC family members and population controls | ||||||||
| Family members | 223 | 442.7 | 124.5 | |||||
| Controls | 813 | 286.4 | 89.41 | |||||
| Empirical P-value | 0.0009 | 0.004 | ||||||
| Unaffected SLIC family members and population controls | ||||||||
| Family members | 132 | 442.6 | 119.6 | |||||
| Controls | 813 | 286.4 | 89.4 | |||||
| Empirical P-value | 0.01 | 0.03 | ||||||
Abbreviations: CNV, copy number variant; NWR, non-word repetition; SLIC, specific language impairment Consortium.
Those metrics that differed significantly between independent cases and population controls were then examined further in affected first-degree relatives and all first-degree relatives compared with population controls. In Table 1, an alternative definition of affection was also explored; independent cases were selected on the basis of NWR >1.5 SD below that expected for their age. Categories in bold had a P-value <0.05.