Background
Methods
Overview of dataset
Phenotype data
SNP genotyping quality control (QC) and imputation
Ancestry assignment and genetic relationships
Polygenic scoring
Description of input GWAS summary statistics
Selection of UK Biobank (UKB) controls
SBayesR PGS weighting
Group | n_all | n_ind | n CNV | % with CNV | No. median | No. mean | ASD/ID CNV del | ASD/ID CNV dup | ASD/ID/DD genes del | ASD/ID/DD genes dup |
---|---|---|---|---|---|---|---|---|---|---|
ASD | 885 | 263 | 330 | 29.72 | 0 | 0.37 | 11 | 4 | 5 | 3 |
FTR | 504 | 134 | 167 | 26.59 | 0 | 0.33 | 0 | 0 | 1 | 0 |
MTR | 752 | 232 | 280 | 30.85 | 0 | 0.37 | 3 | 0 | 3 | 0 |
SIB | 218 | 57 | 68 | 26.15 | 0 | 0.31 | 0 | 0 | 0 | 0 |
UNR | 116 | 37 | 40 | 31.90 | 0 | 0.34 | 0 | 0 | 0 | 0 |
Diagnosed children | |||||||
---|---|---|---|---|---|---|---|
Sample ID | Group | Sex | Type | CNV coordinates | ASD/ID-associated CNV | Reference coordinates | Other information |
CNVs with a critical gene | |||||||
1101366 | ASD | M | Dup | chr17:1,196,088–1,326,656 | 17p13.3 (Miller-Dieker syndrome) region (includes YWHAE and PAFAH1B1)^ | chr17:1,247,833–2,588,909 | Critical gene coordinates: YWHAE: chr17:1,247,569–1,268,350; PAFAH1B1: chr17:2,541,583–2,585,096 |
1101637 | ASD | M | Dup | chr17:29,111,368–30,343,735 | 17q11.2 recurrent region (includes NF1) | chr17:29,097,069–30,264,027 | Critical gene coordinates: chr17:29,422,328–29,701,173 |
CNVs without a critical gene | |||||||
4406214 | ASD | F | Dup | chr15:22,321,690–32,515,100 | 15q11q13 recurrent (PWS/AS) region (BP1-BP3, Class 1) | chr15:22,832,519–28,379,874 | 100.00% overlap |
3305166 | ASD | M | Del | chr15:29,079,105–32,515,100 | 15q13.3 recurrent region (D-CHRNA7 to BP5) (includes CHRNA7 and OTUD7A) | chr15:32,019,621–32,445,405 | 100.00% overlap |
1101486 | ASD | M | Del | chr15:31,007,901–32,515,100 | 15q13.3 recurrent region (D-CHRNA7 to BP5) (includes CHRNA7 and OTUD7A) | chr15:32,019,621–32,445,405 | 100.00% overlap |
1101365 | ASD | M | Del | chr15:31,115,226–32,515,100 | 15q13.3 recurrent region (D-CHRNA7 to BP5) (includes CHRNA7 and OTUD7A) | chr15:32,019,621–32,445,405 | 100.00% overlap |
4406241* | ASD | M | Del | chr16:21,973,913–22,414,463 | Recurrent 16p12.1 microdeletion (neurodevelopmental susceptibility locus) | chr16:21,946,524–22,467,284 | 84.60% overlap |
3305177 | ASD | M | Del | chr16:28,832,565–29,044,745 | 16p11.2 recurrent region (distal, BP2-BP3) (includes SH2B1) | chr16:28,822,635–29,046,499 | 94.78% overlap |
1101491 | ASD | F | Del | chr22:18,877,787–21,461,607 | 22q11.2 recurrent (DGS/VCFS) region (proximal, A-D) (includes TBX1) | chr22:15,912,231–21,465,672 | 99.84% overlap |
4406202 | ASD | F | Del | chrX:6,488,784–8,135,053 | Xp22.31 recurrent region (includes STS) | chrX:6,455,812–8,133,195 | 98.02% overlap |
Parents | |||||||
4411283* | MTR | M | Del | chr16:21,956,457–22,414,463 | Recurrent 16p12.1 microdeletion (neurodevelopmental susceptibility locus) | chr16:21,946,524–22,467,284 | 87.95 |
2215012 | MTR | F | Del | chr22:19,036,154–20,244,259 | 22q11.2 recurrent (DGS/VCFS) region (proximal, A-B) (includes TBX1) | chr22:18,912,231–20,287,208 | 87.86 |
1116571 | MTR | F | Del | chrX:6,456,940–8,135,053 | Xp22.31 recurrent region (includes STS) | chrX:6,455,812–8,133,195 | 99.93 |
PGS calculation
Between-group PGS differences
Over-transmission of common genetic variation for ASD
Relationships between PGS and phenotypes
Multiple testing correction
Copy number variant (CNV) calling
CNV annotation
Results
Characteristics of the Australian Autism Biobank (AAB)
Polygenic risk scoring
Between-group PGS comparisons
Sample ID | Group | Sex | CNV coordinates | Gene | Description | Overlap % of gene | Cytoband |
---|---|---|---|---|---|---|---|
Diagnosed children | |||||||
Deletions | |||||||
1101306* | ASD | F | chr2:148,730,454–148,883,419 | MBD5 | methyl-CpG binding domain protein 5 | 21 | 2q23.1 |
1101211+ | ASD | M | chr10:27,978,030–28,041,669 | MKX | mohawk homeobox | 78 | 10p12.1 |
3305052 | ASD | M | chr19:10,609,319–12,464,434 | ELAVL3 | ELAV like neuron-specific RNA binding protein 3 | 100 | 19p13.2 |
4406296^ | ASD | M | chr20:61,824,507–62,321,517 | KCNQ2 | potassium voltage-gated channel, KQT-like subfamily, member 2 | 100 | 20q13.33 |
4406297^ | ASD | M | chr20:61,802,599–62,268,955 | KCsNQ2 | potassium voltage-gated channel, KQT-like subfamily, member 2 | 100 | 20q13.33 |
1101417 | ASD | M | chr2:32,277,654–32,818,823 | SPAST | spastin | 100 | 2p22.3 |
1101240 | ASD | M | chr4:6,104,865–7,415,038 | KIAA0232 | KIAA0232 | 100 | 4p16.1 |
4406214 | ASD | F | chr15:22,321,690–32,515,100 | GABRB3 | gamma-aminobutyric acid (GABA) A receptor, beta 3 | 100 | 15q12 |
Parents transmitting CNVs | |||||||
1116306* | Mother | F | chr2:148,730,454–148,883,419 | MBD5 | methyl-CpG binding domain protein 5 | 21 | 2q23.1 |
1116211+ | Mother | F | chr10:27,978,030–28,041,669 | MKX | mohawk homeobox | 78 | 10p12.1 |
4411296^ | Mother | F | chr20:61,802,599–62,321,517 | KCNQ2 | potassium voltage-gated channel, KQT-like subfamily, member 2 | 100 | 20q13.33 |