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. Author manuscript; available in PMC: 2013 Mar 16.
Published in final edited form as: Cell. 2012 Mar 16;148(6):1223–1241. doi: 10.1016/j.cell.2012.02.039

Table 1. Analysis of pathogenic CNVs across multiple diagnostic categories: intellectual ability, Autism Spectrum Disorders, schizophrenia and bipolar disorder.

We analyzed 11 CNV loci where replicated evidence of association with schizophrenia and/or developmental disorders is available from multiple large-scale studies. We compared the frequency of each CNV loci in four major categories of neuropsychiatric disorders including intellectual disability (ID)/developmental delay (DD)/congenital malformations (CM), autism spectrum disorders (ASD), schizophrenia (SD) and bipolar disorder (BD)/Recurrent Depression, with its frequency in a large combined set of controls. We did not attempt a formal meta-analysis, as some studies did not include CNV data on both cases and controls. We present results with a pooled analysis of available CNV frequency data from different studies by performing a simple Fisher’s Exact Test and reporting odds ratio. We excluded overlapping individuals in different studies before doing tests for individual loci. Formal meta-analyses results are available for some of the published loci (Levinson et al., 2011) and the odds ratios (OR) and p-values reported for loci in the previous studies are similar to results reported here. Exonic deletions at the NRXN1 gene, also implicated as a risk factor for schizophrenia, were not analyzed as the CNVs affecting them are usually non-recurrent and much smaller than 500 kb and can be missed with the lower-resolution array studies included in the current analysis. See Supplemental Information for the references in the table.

CNV Locus Position (Mb) Disease category Frequency in combined cases Frequency in combined controls P value Odds Ratio [95% CI] Case References Control References
1q21.1 deletion 145.0–146.3 MR/DD/CM 0.27% (102/ 38,330) 0.02% (16/ 75,505) 1.9 × 10−32 12.6 [7.4–21.3] Mefford et al 2008; Brunettipierri et al 2008; Cooper et al 2011 Vacic et al 2011; Grozeva et al 2011; Grozeva et al 2010; Rucker et al 2011; Sanders et al 2011; Levinson et al 2011; Cooper et al 2011
ASD 0.03% (1/ 3032) 0.02% (16/ 75,505) 0.49 1.6 [0.2–11.7] Bucan et al 2009; Sanders et al 2011; Pinto et al 2010
SCZ 0.17% (21/ 12,174) 0.02% (16/ 75,505) 1.3 × 10−9 8.1 [4.3–15.6] Vacic et al 2011; Levinson et al 2011
BD & Recurrent Depression 0.02% (2/ 8264) 0.02% (16/ 75,505) 0.69 1.1 [0.3–5.0] Malhotra et al 2011; Priebe et al 2011; Grozeva et al 2010; BiGS; Rucker et al 2011
1q21.1 duplication 145.0–146.3 MR/DD/CM 0.14% (55/ 38,330) 0.03% (19/ 57,730) 2.7 × 10−9 4.4 [2.6–7.4] Mefford et al 2008; Brunetti-pierri et al 2008; Cooper et al 2011 Vacic et al 2011; Grozeva et al 2010; Rucker et al 2011; Sanders et al 2011; Levinson et al 2011; Cooper et al 2011
ASD 0.26% (8/ 3032) 0.03% (19/ 57,730) 3.6 × 10−5 8.0 [3.5–18.4] Bucan et al 2009; Sanders et al 2011; Pinto et al 2010
SCZ 0.14% (13/ 9365) 0.03% (19/ 57,730) 0.0002 4.2 [2.1–8.6] Vacic et al 2011; Levinson et al 2011
BD & Recurrent Depression 0.10% (7/ 7382) 0.03% (19/ 57,730) 0.02 2.9 [1.2–6.9] Malhotra et al 2011; Grozeva et al 2010; BiGS; Rucker et al 2011
3q29 deletion 197.2–198.4 MR/DD/CM 0.07% (20/ 30465) 0.002% (1/ 63,649) 2.3 × 10−9 41.8 [5.6–311.6] Ballif et al 2008; Cooper et al 2011 Vacic et al 2011; Grozeva et al 2011; Grozeva et al 2010; Sanders et al 2011; Levinson et al 2011; Mulle et al 2010
ASD 0.05% (1/ 2120) 0.002% (1/ 63,649) 0.06 30.0 [1.9–480.4] Sanders et al, 2011; Pinto et al 2010
SCZ 0.10% (10/ 10,123) 0.002% (1/ 63,649) 2.3 × 10−8 63.0 [8.1–491.7] Vacic et al 2011; Levinson et al 2011; Mulle et al 2010
BD 0.04% (2/ 4659) 0.002% (1/ 63,649) 0.01 27.3 [2.5–301.5] Malhotra et al 2011; Grozeva et al 2010; BiGS
7q11.23 WBS deletion 72.4–73.8 MR/DD/CM 0.27% (42/15767) 0% (0/ 16,257) 1.2 × 10−13 Cooper et al 2011 Vacic et al 2011; Grozeva et al 2010; Sanders et al 2011; Cooper et al 2011; BiGS
ASD 0% (0/2120) 0% (0/ 16,257) 1 Sanders et al, 2011; Pinto et al 2010
SCZ 0% (0/8701) 0% (0/ 16,257) 1 Vacic et al 2011; Levinson et al 2011;
BD 0% (0/4659) 0% (0/ 16,257) 1 Malhotra et al 2011; Grozeva et al 2010; BiGS
7q11.23 WBS duplication 72.4–73.8 MR/DD/CM 0.10% (16/15767) 0% (1/ 16,257) 0.0001 16.5 [2.2–124.5] Cooper et al 2011 Vacic et al 2011; Grozeva et al 2010; Sanders et al 2011; Cooper et al 2011; BiGS
ASD 0.19% (4/2120) 0% (1/ 16,257) 0.0008 30.7 [3.4–275.1] Sanders et al, 2011; Pinto et al 2010
SCZ 0.05% (4/8701) 0% (1/ 16,257) 0.053 7.5 [0.8–66.9] Vacic et al 2011; Levinson et al 2011;
BD 0% (0/4659) 0% (1/ 16,257) 1 Malhotra et al 2011; Grozeva et al 2010; BiGS
VIPR2 (7q36.3) duplication 158.4–158.8 MR/DD/CM 0.06% (11/ 18,499) Sanders et al 2011; Levinson et al 2011; Grozeva et al 2010.
ASD 0.13% (3/ 2234) 0.06% (11/ 18,499) 0.18 2.3 [0.63–8.1] Sanders et al 2011; Vacic et al 2011
SCZ 0.19% (14/ 7336) 0.06% (11/ 18,499) 0.006 3.2 [1.5–7.1] Levinson et al 2011
BD 0.04% (2/ 4659) 0.06% (11/ 18,499) 1 Malhotra et al 2011; Vacic et al 2011; Grozeva et al 2010
15q11.2 deletion 20.3–20.6 MR/DD/CM 0.51% (180/ 35,353) 0.27% (201/ 75,486) 4.9 × 10−10 1.9 [1.6–2.3] Doornbos et al 2009; Mefford et al 2009; Burnside et al 2011; Cooper et al 2011 Vacic et al 2011; Sanders et al 2011; Grozeva et al 2011; Rucker et al 2011; Cooper et al 2011; Kirov et al 2009; Levinson et al 2011
ASD 0.09% (2/ 2120) 0.27% (201/ 75,486) 0.19 0.3 [0.1–1.4] Pinto et al 2010; Sanders et al 2011
SCZ 0.57% (72/ 12,665) 0.27% (201/ 75,486) 2.2 × 10−7 2.1 [1.6–2.8] Vacic et al 2011; Kirov et al 2009; Levinson et al 2011
BD & Recurrent Depression 0.22% (18/8264) 0.27% (201/ 75,486) 0.49 Priebe et al 2011; Malhotra et al 2011; BiGS; Grozeva et al 2010; Rucker et al 2011
15q11.2-13.1 duplication including PWS critical region 20.8–26.2 MR/DD/CM 0.17% (27/ 15767) 0.009% (5/ 53,832) 2.2 × 10−13 18.5 [7.1–47.9] Cooper et al 2011 Vacic et al 2011; Cooper et al 2011; Glessner et al 2009; Sanders et al 2011; Ingason et al 2011
ASD 0.39% (17/ 4315) 0.009% (5/ 53,832) 1.1 × 10−15 42.6 [15.7–115.5] Glessner et al 2009; Sanders et al 2011; Pinto et al 2010
SCZ 0.05% (4/ 8384) 0.009% (5/ 53,832) 0.02 5.1 [1.4–19.1] Vacic et al 2011; Ingason et al 2011
BD 0% (0/ 4659) 0.009% (5/ 53,832) 1 Malhotra et al 2011; Grozeva et al 2010; BiGS
15q13.3 deletion 28.7–30.2 MR/DD/CM 0.26% (68/ 25,647) 0.02% (13/ 74,106) 6.1 × 10−28 15.1 [8.4–27.4] Van bon et al 2009; Sharp et al 2008; Miller et al 2009; Cooper et al 2011 Vacic et al 2011; Grozeva et al 2011; Grozeva et al 2010; Rucker et al 2011; Sanders et al 2011; Cooper et al 2011; Levinson et al 2011
ASD 0.19% (4/ 2120) 0.02% (13/ 74,106) 0.001 10.8 [3.5–33.1] Sanders et al 2011; Pinto et al 2010
SCZ 0.19% (22/ 11,689) 0.02% (13/ 74,106) 2.1 × 10−11 10.7 [5.4–21.3] Vacic et al 2011; Levinson et al 2011
BD & Recurrent Depression 0.01% (1/ 7382) 0.02% (13/ 74,106) 1 Malhotra et al 2011; Grozeva et al 2010; Rucker et al 2011
16p13.11 duplication 15.4–16.2 MR/DD/CM 0.30% (99/ 32,413) 0.13% (81/ 62,973) 8.4 × 10−9 2.4 [1.8–3.2] Ramalingam et al 2011; Nagamani et al 2011; Mefford et al 2009; Cooper et al 2011 Vacic et al 2011; Grozeva et al 2011; Rucker et al 2011; Sanders et al 2011; Cooper et al 2011; Ingason et al 2009
ASD 0.19% (4/ 2120) 0.13% (81/ 62,973) 0.36 1.5 [0.5–4.0] Sanders et al 2011; Pinto et al 2010
SCZ 0.25% (13/ 5147) 0.13% (81/ 62,973) 0.03 2.0 [1.1–3.5] Vacic et al 2011; Ingason et al 2009
BD & Recurrent Depression 0.07% (6/ 7382) 0.13% (81/ 62,973) 0.38 0.8 [0.4–1.9] Malhotra et al 2011; BiGS; Grozeva et al 2010; Rucker et al 2011
16p11.2 deletion 29.5–30.2 MR/DD/CM 0.41% (64/ 15767) 0.04% (25/ 56,752) 7.3 × 10−24 9.2 [5.8–14.7] Cooper et al 2011 Grozeva et al 2011; Glessner et al 2009; Rucker et al Sanders et al 2011; Cooper et al 2011; Levinson et al 2011
ASD 0.42% (18/ 4315) 0.04% (25/ 56,752) 2.0 × 10−10 9.5 [5.2–17.4] Glessner et al 2009; Sanders et Pinto et al 2010
SCZ 0.04% (4/ 9890) 0.04% (25/ 56,752) 1 0.9 [0.3–2.6] Levinson et al 2011
BD & Recurrent Depression 0.07% (6/ 8427) 0.04% (25/ 56,752) 0.28 1.6 [0.7–3.9] Priebe et al 201; Mccarthy et al 2009; Rucker et al 2011
16p11.2 duplication 29.5–30.2 MR/DD/CM 0.18% (18/ 15,767) 0.03% (19/ 56,752) 2.2 × 10−8 3.4 [1.8–6.5] Cooper et al 2011 Grozeva et al 2011; Glessner et al 2009; Rucker et al Sanders et al 2011; Cooper et al 2011; Levinson et al 2011
ASD 0.39% (17/ 4315) 0.03% (19/ 56,752) 6.2 × 10−11 11.8 [6.1–22.7] Glessner et al 2009; Sanders et Pinto et al 2010
SCZ 0.31% (31/ 9890) 0.03% (19/ 56,752) 3.2 × 10−14 9.4 [5.3–16.6] Levinson et al 2011
BD & Recurrent Depression 0.13% (11/ 8427) 0.03% (19/ 56,752) 0.0008 3.9 [1.9–8.2] Priebe et al 2011; Mccarthy et al 2009; Rucker et al 2011
17p12/HNPP deletion 14–15.4 MR/DD/CM 0.02% (3/ 15767) 0.02% (14/ 59,086) 1 0.8 [0.2–2.8] Cooper et al 2011 Vacic et al 2011; Cooper et al 2011; Grozeva et al 2011; Sanders et al 2011; Kirov et al 2009
ASD 0.09% (2/ 2120) 0.02% (14/ 59,086) 0.1 4.0 [0.9–17.5] Sanders et al 2011; Pinto et al 2010
SCZ 0.14% (8/ 5891) 0.02% (14/ 59,086) 0.0004 5.7 [2.4–13.7] Vacic et al 2011; Kirov et al 2009
BD 0.05% (3/ 5541) 0.02% (14/ 59,086) 0.17 2.3 [0.7–8.0] Priebe et al 2011; Malhotra et al 2011; BiGS; Grozeva et al 2010
17q12 deletion 31.9–33.2 MR/DD/CM 0.10% (32/ 31,516) 0.006% (4/ 68,131) 1.4 × 10−12 17.3 [6.1–49.0] Cooper et al 2011; Moreno-deluca 2010 Vacic et al 2011; Grozeva et al 2011; Sanders et al 2011; Moreno-deluca 2010; Cooper et al 2011.
ASD 0.09% (2/ 2120) 0.006% (4/ 68,131) 0.01 16.0 [2.9–87.9] Sanders et al 2011; Pinto et al 2011
SCZ 0.06% (4/ 7142) 0.006% (4/ 68,131) 0.004 9.5 [2.4–38.2] Vacic et al 2011; Moreno-deluca 2010
BD & Recurrent Depression 0% (0/ 4659) 0.006% (4/ 68,131) 1 Malhotra et al 2011; BiGS; Grozeva et al 2010
22q11.21 deletion 17.1–18.7 MR/DD/CM 0.61% (96/ 15767) 0% (0/ 70,739) 8.4 × 10−72 Cooper et al 2011 Vacic et al 2011; Grozeva et al 2011; Rucker et al 2011; Sanders et al 2011; Cooper et al 2011; Levinson et al 2011
ASD 0.07% (2/ 3032) 0% (0/ 70,739) 0.002 Bucan et al 2009; Sanders et al 2011; Pinto et al 2010
SCZ 0.30% (36/ 12,202) 0% (0/ 70,739) 1.0 × 10−30 Vacic et al 2011; Levinson et al 2011
BD & Recurrent Depression 0.05% (4/ 7382) 0% (0/ 70,739) 8.0 × 10−5 Malhotra et al 2011; Grozeva et al 2010; BiGS; Rucker et al 2011
22q11.2 duplication 17.1–18.7 MR/DD/CM 0.32% (50/ 15767) 0.08% (23/ 27,133) 5.9 × 10−8 3.7 [2.3–6.1] Cooper et al 2011 Vacic et al 2011; Grozeva et al 2010; Sanders et al 2011; Cooper et al 2011; Glessner et al 2009; ISC et al 2008; Rucker et al 2011
ASD 0.28% (12/ 4315) 0.08% (23/ 27,133) 0.002 3.3 [1.6–6.6] Glessner et al 2009; Sanders et al 2011; Pinto et al 2010
SCZ 0.03% (3/ 8701) 0.08% (23/ 27,133) 0.17 0.4 [0.1–1.4] Vacic et al 2011; MGS; ISC et al 2008
BD & Recurrent Depression 0.05% (4/ 7382) 0.08% (23/ 27,133) 0.49 0.6 [0.2–1.8] Malhotra et al 2011; Grozeva et al 2010; BiGS; Rucker et al 2011