Background
Methods
Study population
SNV calling
CNV calling
Phenotypic information
Statistical analysis
Results
Demographic data
CMA probands | WES probands | CMA and WES probands | |
---|---|---|---|
Total (n) | 996 | 808 | 674 |
Average diagnosis age (SD) | 8.2 (8.4) | 7.9 (8.3) | 8.0 (8.5) |
Females (n, (%)) | 298 (30%) | 229 (28%) | 185 (27%) |
Average diagnosis age (SD) | 8.8 (9.2) | 8.6 (8.9) | 9.0 (9.5) |
Males (n, (%)) | 698 (70%) | 579 (72%) | 489 (72%) |
Average diagnosis age (SD) | 7.9 (8.1) | 7.6 (8.0) | 7.6 (8.1) |
Birth characteristics and comorbidities | CMA probands (n = 996) | WES probands (n = 808) | ||
---|---|---|---|---|
n (%) | Average diagnosis age (y) for ASD (SD) | n (%) | Average diagnosis age (y) for ASD (SD) | |
HC—large1 | 40 (5%) | 7.9 (7.3) | 30 (5%) | 8.4 (7.7) |
HC—small2 | 87 (11%) | 4.6 (5.9) | 73 (11%) | 4.0 (4.4) |
Large for gestational age3 | 38 (5%) | 7.6 (7.7) | 30 (4%) | 5.2 (5.7) |
Small for gestational age4 | 37 (5%) | 4.1 (6.1) | 35 (5%) | 4.3 (6.3) |
Congenital anomalies | 74 (11%) | 2.9 (4.9) | 57 (10%) | 3.1 (4.7) |
Motor function disorders | 55 (5%) | 4.8 (5.0) | 43 (5%) | 4.6 (4.8) |
Scholastic skill disorders | 155 (16%) | 5.1 (5.6) | 121 (15%) | 5.2 (6.2) |
Speech/language disorders | 133 (13%) | 4.8 (5.8) | 102 (13%) | 4.6 (5.1) |
ADHD | 203 (20%) | 8.4 (7.4) | 160 (20%) | 7.7 (7.2) |
Anxiety disorder | 29 (3%) | 8.8 (6.5) | 20 (2%) | 9.5 (7.0) |
Epilepsy | 309 (31%) | 5.5 (7.2) | 255 (31%) | 5.5 (7.2) |
Intellectual disability | 474 (48%) | 6.5 (7.0) | 381 (47%) | 6.5 (7.1) |
OCD | 79 (8%) | 9.0 (7.4) | 70 (9%) | 9.6 (7.8) |
Psychotic disorders | 86 (9%) | 13.9(10.2) | 67 (8%) | 11.7 (9.8) |
Genetic findings
Chromosomal disorder | Number identified |
---|---|
1p36 microdeletion syndrome | 1 |
1q21.1 duplication syndrome | 3 |
1q43q44 microdeletion syndrome | 1 |
2q33.1 deletion syndrome (Glass syndrome; includes SATB2) | 1 |
2q37 deletion syndrome | 4 |
3q29 deletion syndrome | 1 |
Cri du chat syndrome (5p15 deletion) | 1 |
Williams-Beuren syndrome (7q11.23 deletion) | 2 |
Jacobsen syndrome (11q deletion syndrome) | 1 |
Prader–Willi syndrome/Angelman syndrome (15q11q13 deletion) | 2 |
15q11q13 duplication syndrome | 8 |
15q13.3 deletion syndrome (includes OTUD7A and CHRNA7) | 3 |
ART-16 syndrome (16p13.3 terminal deletion) | 1 |
16p13.11 deletion syndrome | 3 |
16p13.11 duplication1 | 2 |
16p12.1 microdeletion1 | 2 |
16p11.2p12.2 microduplication syndrome | 1 |
Distal 16p11.2 deletion (includes SH2B1) | 1 |
16p11.2 deletion syndrome (proximal, BP4-BP5) | 3 |
16p11.2 duplication syndrome (proximal, BP4-BP5) | 1 |
Potocki-Lupski syndrome (17p11.2 duplication; includes RAI1) | 1 |
17q12 duplication syndrome | 2 |
22q11.2 deletion syndrome (Velo‐cardio‐facial syndrome/DiGeorge syndrome) | 4 |
22q11.2 duplication syndrome | 1 |
Distal 22q11.2 deletion (D-E) | 1 |
Phelan-McDermid syndrome (22q13.3 deletion; includes SHANK3) | 3 |
Xp22.31 deletion | 2 |
Comorbidities and birth characteristics of the probands
WES probands with pdSNV ASC102 list n (%) | CMA probands with pdCNV n (%) | WES and CMA probands with pdCNV or pdSNV ASC102 list n (%) | |
---|---|---|---|
Total (%) | 69 (9%) | 105 (11%) | 123 (18%) |
Average diagnosis age (SD) | 7.3 (7.3) | 7.1 (8.1) | 6.4 (7.4) |
Females (n, (%)) | 20 (9%) | 36 (12%) | 35 (19%) |
Average diagnosis age (SD) | 8.2 (7.0) | 69 (7.5) | 6.2 (6.6) |
Males (n, (%)) | 49 (8%) | 69 (10%) | 88 (18%) |
Average diagnosis age (SD) | 6.9 (7.5) | 6.7 (7.5) | 6.9 (7.6) |
Phenotypes | WES probands with pdSNV (n = 69) ASC102 list n (%) | CMA probands with pdCNV (n = 105) n (%) | WES and CMA probands with pdCNV or pdSNV (n = 123) AS102 list n (%) |
---|---|---|---|
HC—large1 | 4 (6%) | 4 (4%) | 6 (5%) |
HC—small2 | 4 (6%) | 13 (12%) | 14 (11%) |
Large for gestational age3 | 0 (0%) | 2 (2%) | 1 (1%) |
Small for gestational age4 | 0 (0%) | 7 (7%) | 5 (4%) |
Congenital anomalies | 3 (4%) | 18 (17%) | 15 (12%) |
Motor function disorders | 2 (3%) | 8 (8%) | 7 (6%) |
Scholastic skill disorders | 11 (16%) | 25 (24%) | 27 (22%) |
Speech/language disorders | 7 (10%) | 18 (17%) | 16 (13%) |
ADHD | 11 (16%) | 23 (22%) | 25 (20%) |
Anxiety disorder | 1 (1%) | 2 (2%) | 2 (2%) |
Epilepsy | 30 (43%) | 34 (32%) | 49 (40%) |
Intellectual disability | 47 (68%) | 58 (55%) | 75 (61%) |
OCD | 3 (4%) | 8 (8%) | 8 (7%) |
Psychotic disorders | 4 (6%) | 12 (11%) | 14 (11%) |
Phenotypes | WES probands with pdSNV ASC102 list (n = 69) | WES probands with pdSNV ASC102 + DGR list (n = 144) | ||||
---|---|---|---|---|---|---|
OR | 95% CI | p value | OR | 95% CI | p value | |
HC—large1 | 0.86 | (0.53,5.02) | 0.27 | 1.73 | (0.67,3.97) | 0.22 |
HC—small2 | 0.67 | (0.20,1.73) | 0.46 | 1.46 | (0.76,2.64) | 0.23 |
Large for gestational age3 | – | – | – | 0.83 | (0.24,2.19) | 0.73 |
Small for gestational age4 | – | – | – | 0.69 | (0.20,1.79) | 0.49 |
Congenital anomalies | 0.57 | (0.14,1.64) | 0.36 | 0.80 | (0.34,1.66) | 0.58 |
Motor function disorders | 0.51 | (0.08,1.70) | 0.36 | 0.99 | (0.40,2.16) | 0.99 |
Scholastic skill disorders | 1.08 | (0.52,2.05) | 0.82 | 0.75 | (0.41,1.28) | 0.31 |
Speech/language disorders | 0.77 | (0.31,1.62) | 0.52 | 0.95 | (0.52,1.64) | 0.85 |
ADHD | 0.75 | (0.37,1.41) | 0.40 | 0.99 | (0.61,1.57) | 0.96 |
Anxiety disorder | 0.55 | (0.03,2.74) | 0.56 | 0.56 | (0.09,1.97) | 0.44 |
Epilepsy | 1.76 | (1.06,2.89) | 0.03* | 1.51 | (1.02,2.22) | 0.03* |
Intellectual disability | 2.60 | (1.55,4.48) | < 0.01* | 2.62 | (1.78,3.91) | < 0.01* |
OCD | 0.45 | (0.11,1.27) | 0.19 | 0.37 | (0.13,0.85) | 0.03* |
Psychotic disorders | 0.66 | (0.20,1.66) | 0.43 | 0.67 | (0.29,1.37) | 0.31 |
Phenotypes | CMA probands with pdCNV (n = 105) | WES and CMA probands with pdSNV or pdCNV ASC102 list (n = 123) | WES and CMA probands with pdSNV or pdCNV ASC102 + DGR list (n = 182) | ||||||
---|---|---|---|---|---|---|---|---|---|
OR | 95% CI | p value | OR | 95% CI | p value | OR | 95% CI | p value | |
HC—large1 | 0.97 | (0.28,2.52) | 0.96 | 1.31 | (0.47,3.15) | 0.58 | 1.42 | (0.60,3.17) | 0.40 |
HC—small2 | 1.58 | (0.80,2.93) | 0.16 | 1.45 | (0.74,2.71) | 0.26 | 1.67 | (0.94,2.92) | 0.07 |
Large for gestational age3 | 0.46 | (0.07,1.54) | 0.29 | 0.17 | (0.01,0.82) | 0.08 | 0.64 | (0.21,1.61) | 0.40 |
Small for gestational age4 | 2.05 | (0.80,4.58) | 0.10 | 1.12 | (0.36,2.82) | 0.83 | 1.82 | (0.78,4.05) | 0.16 |
Congenital anomalies | 2.99 | (1.61,.36) | < 0.01* | 1.89 | (0.96,3.56) | 0.06 | 1.72 | (0.93,3.12) | 0.08 |
Motor function disorders | 1.48 | (0.63,3.07 | 0.33 | 1.27 | (0.50,2.86) | 0.59 | 1.44 | (0.66,3.00) | 0.34 |
Scholastic skill disorders | 1.82 | (1.10,2.92) | 0.02* | 1.93 | (1.16,3.14) | < 0.01* | 1.40 | (0.87,2.21) | 0.16 |
Speech/language disorders | 1.38 | (0.78,2.33) | 0.25 | 1.08 | (0.59,1.90) | 0.79 | 1.27 | (0.76,2.07) | 0.34 |
ADHD | 1.11 | (0.67,1.78) | 0.68 | 1.14 | (0.69,1.83) | 0.61 | 1.10 | (0.71,1.68) | 0.66 |
Anxiety disorder | 0.59 | (0.09,2.03) | 0.48 | 0.62 | (0.10,2.28) | 0.54 | 0.62 | (0.14,1.94) | 0.45 |
Epilepsy | 1.06 | (0.68,0.63) | 0.78 | 1.56 | (1.04,2.33) | 0.03* | 1.53 | (1.07,2.18) | 0.02* |
Intellectual disability | 1.41 | (0.94,2.12) | 0.10 | 2.16 | (1.14,3.24) | < 0.01* | 2.37 | (1.67,3.37) | < 0.01* |
OCD | 0.93 | (0.40,1.89) | 0.86 | 0.69 | (0.30,1.43) | 0.35 | 0.76 | (0.39,1.41) | 0.41 |
Psychotic disorders | 1.40 | (0.70,2.59) | 0.30 | 1.44 | (0.74,2.66) | 0.26 | 1.10 | (0.60,1.46) | 0.74 |
Phenotypes | CMA probands without ID (n = 522) with pdCNV (n = 47, 9%) | CMA probands with ID (n = 474) with pdCNV (n = 58, 12%) | ||||
---|---|---|---|---|---|---|
OR | 95% CI | p value | OR | 95% CI | p value | |
HC—large1 | 1.74 | (0.39,5.48) | 0.40 | 0.42 | (0.02,2.11) | 0.40 |
HC—small2 | 0.24 | (0.01,1.19) | 0.17 | 2.85 | (1.31,5.94) | < 0.01* |
Large for gestational age3 | 0.87 | (0.14,3.13) | 0.85 | – | – | – |
Small for gestational age4 | 2.05 | (0.46,6.67) | 0.28 | 2.01 | (0.55,5.81) | 0.23 |
Congenital anomalies | 3.71 | (1.36,9.23) | 0.01* | 2.46 | (1.09,5.26) | 0.02* |
Motor function disorders | 0.83 | (0.13,2.94) | 0.81 | 1.99 | (0.71,4.86) | 0.15 |
Scholastic skill disorders | 2.01 | (0.90,4.14) | 0.07 | 1.61 | (0.83,3.00) | 0.14 |
Speech/language disorders | 2.14 | (0.92,4.54) | 0.06 | 0.92 | (0.41,1.89) | 0.83 |
ADHD | 1.43 | (0.70,2.75) | 0.30 | 0.89 | (0.41,1.78) | 0.76 |
Anxiety disorder | 1.09 | (0.17,4.02) | 0.91 | – | – | – |
Epilepsy | 1.21 | (0.57,2.40) | 0.60 | 0.86 | (0.49,1.51) | 0.61 |
OCD | 1.50 | (0.55,3.51) | 0.38 | 0.47 | (0.08,1.63) | 0.31 |
Psychotic disorders | 1.24 | (0.41,3.07) | 0.67 | 1.63 | (0.63,3.68) | 0.27 |