Table 3.
Overview of studies using the SSC collection
| Reference | Bio-collection | Samples | Number | Study | Findings |
|---|---|---|---|---|---|
| [296] | SSC | Genomic data | 2760 subjects | CNV analysis | No association found between conception-assisted reproduction and risk of ASD |
| [297] | SSC | Lymphoblasts | 900 subjects | Sequencing study | Rare functional variants of TSC1/TSC2 did not show association with ASD |
| [298] | SSC | Genomic data | 965 subjects (SSC) | Integrative analysis | Integrative analysis of data from 4 exome sequencing studies revealed enrichment of genes involved in chromatin remodelling and transcription in ASD patients |
| [88] | SSC | Blood | 3730 subjects | Genotype-phenotype | Subtype of autism was caused by mutations to CHD8, of which 15 were found. |
| [299] | SSC | Blood | 259 subjects | CNV analysis | Paired duplications mark cryptic inversions and other complex structural variations in CNV data. |
| [300] | SSC | Blood | 552 subjects (total) 412 subjects (SSC) |
Transcriptome analysis | Neuron development, nitric oxide signalling, neurogenesis and skeletal development were found outliers amongst ASD patients in TGEN cohort, whereas outliers were found in neurogenesis in ASD patients from SSC cohort |
| [301] | SSC | Blood and lymphoblasts | 99 families | CNV analysis | 55 potential pathogenic CNVs were identified and validated. 20% were considered rare when compared to the database of genomic variants. CNVs found in lymphoblast DNA but not in blood, suggesting pre-existing mutations may have been present in initial lymphoblast cells |
| [302] | SSC AGRE |
Blood urine | 12600 subjects (total) 1887 subjects (SSC) 752 subjects (AGRE) |
Association study | TMLHE found to have high levels of deletion in male-male multiplex families (1 in 190) and deficiency of this gene could be a susceptibility factor for ASD. |
| [303] | SSC | Genomic and exomic data | Taken from earlier studies [60, 61, 70] | Genotype-phenotype study | Mutations in ASD candidate genes have greatest impact on pyramidal neurons, cortical neurons and medium spiny neurons. Truncating de novo mutations play a small role in high-functioning cases. The greater the functional disruption of genes, the more severe the phenotypes are. |
| [304] | SSC | Blood | 2575 subjects | GWAS | Reducing phenotypic heterogeneity within the cohort did not have a significant effect on increasing genetic homogeneity. |
| [305] | SSC AGRE |
Blood | 14989 subjects (total) 5981 subjects (AGRE) 1815 subjects (SSC) |
GWAS | CNVs found in SEMA5 regulated gene network found to be associated with ASD |
| [86] | SSC | Blood | 13,804 subjects | WES | 104 genes were implicated in 5% of ASD cases, where they are involved in transcription, chromatin remodelling and synapse formation. |
| [59] | SSC | Blood | 2963 subjects | WES | De novo INDELS primarily originate from father, frameshift INDELS associated with ASD, Frameshift INDELS more frequent in females. RIMS1 and KMT2E found to be associated with ASD |
| [306] | SSC | Blood | 8 subjects | Methods Paper | WGS data more effective than WES for detection of INDELS. x60 sequencing required to recover 95% of detected Indels |
| [307] | SSC | Genomic data | 2066 subjects | Homozygosity study | In ASD simplex families, increased runs of homozygosity is associated with Intellectual disability |
| [308] | SSC | Blood | 1227 subjects (total) 350 subjects (SSC) |
CNV analysis | CNV burden correlates to certain disorders; high CNV burden to Intellectual disability and low CNV burden to dyslexia |
| [178] | SSC AGRE |
Blood | 3168 subjects (total) 2478 subjects (SSC) 719 subjects (AGRE) |
Rearrangement hotspot study | 1q21 duplications found to be associated with Autism. CNVs identified in CHD1L, ACACA, DPP10, PLCB1, TRPM1, NRXN1, FHIT and HYDIN enriched in ASD. Duplications linked to decreased non-verbal IQ and duplications linked to severity of ASD. |
| [149] | SSC | IPSCs and lymphoblasts | 1041 subjects | Disease modelling study | Disruption of TRPC6 causes disruption in human neurons and linked to a non-syndromic form of ASD. First Study to use Patent-derived IPSCs to model non-syndromic form of ASD |
| [309] | SSC AGRE |
Blood | 2975 subjects (total) 1429 subjects (SSC) 14 subjects (AGRE |
GWAS sequencing | Rare variants in synaptic genes associated with ASD. Loss of function in candidate genes a major risk factor for ASD. |
| [310] | SSC TASC |
Blood | 932 families (total) | Method paper | Transmission and de novo association(TADA) is a method that incorporates WES data, as well as inherited variants, and variants identified between cases and controls |
| [311] | SSC | Exome data | 597 subjects | Method description | Association was found between ASD and rare variants of the gene ABCA7 in exome data |
| [312] | SSC | Blood | 15479 subjects (total) 9479 subjects (SSC) |
Transmission analysis | Demonstration that high and low IQs could be distinguished by LGD load in respective gene targets. Transmission of rare variants with low LGD load occurs more often to affected offspring. Biased transmission towards children with low IQ |
| [61] | SSC | Blood | 1478 subjects | WES | Gene disrupting mutations were twice as frequent in ASD subjects compared to controls. Genes disrupted were associated with Fragile X Protein FMRP. |
| [121] | SSC | Blood | 762 subjects | CNV study | Female subjects showed a higher mutational burden before developing ASD. |
| [313] | SSC | Blood | 720 subjects | Association study | Association was found between gene SLC25A12 and restricted and repetitive behaviour. |
| [314] | SSC | Blood | 2106 families (TOTAL) 965 families(SSC) |
Common variation study | Multiple common variants of genes additively contribute to ASD risk. Simplex families found to closely follow additive model compared to multiplex families |
| [315] | SSC | Blood | 285 subjects | Transcriptomic study | Enriched genes found in long term potentiation/depression, Notch signalling and neurogenesis amongst ASD Patients. 55 gene prediction model performed well on male subjects, but not female subjects |
| [316] | SSC | Blood | 58 subjects | Transcriptomic study | Upregulation of spliceosome, mitochondrial and ribosomal pathways and downregulation of neuroreceptor-ligand, immune response and calcium signalling pathways in ASD patients compared to controls |
| [317] | SSC | Genomic data | 78349 subjects (total) 3080 subjects (SSC) |
SNP study | 17–29% of variance in liability explained by SNPS. Genetic correlation found between disorders; High: Schizophrenia and bipolar disorder Moderate: Schizophrenia and major depressive disorder, major depressive disorder and ADHD, major depressive disorder and bipolar disorder Low: Schizophrenia and ASD |
| [60] | SSC | Genomic Data | 1784 subjects | CNV study | De novo duplications and deletions are major contributors to ASD. Females shown to have a greater genetic resistance to autism. |
| [318] | SSC AGRE TASC |
Blood | 6970 subjects (total) 806 subjects (AGRE) 996 subjects (TASC) 563 subjects (AGRE) |
WES | 2-fold enrichment of complete knockout of autosomal genes with low LoF variation, and 1.5-fold enrichment for rare hemizygous knockout in males. Both contribute 3 and 2% to ASD risk, respectively. |
| [63] | SSC | Lymphoblasts | 386 subjects | CNV study | Recurrent and rare de novo CNVs were discovered to alter gene expression in chromosome regions 3q27, 3p13, 3p26, 2p15, 16p11.2 and 7q11.23. |
| [129] | SSC | IPSCs | 12 subjects | Disease modelling | Overexpression of FOXG1 was linked to increased head circumference and ASD severity in idiopathic autism subjects. An overabundance of inhibitory neurons in ASD cell lines was also found. |
| [319] | SSC | Genomic and clinical data | 2478 subjects | Gene-environment study | Individuals with ASD-associated CNVs were more susceptible to effects of febrile episodes and maternal infection during pregnancy and have impact on behavioural outcomes |
| [320] | SSC | Blood | 10118 (TOTAL) 1974 (SSC) |
Genetic association | Higher prevalence of SLC12A5 variants containing altered CpG sites amongst ASD patients. |
| [321] | SSC DNSB |
Blood | 2418 subjects (SSC) 1353 subjects (DSNB) |
CNV analysis | 17q12 deletion identified as a CNV variant that confers high risk of ASD and Schizophrenia |
| [322] | SSC AGRE |
Genomic data | 49167 subjects (total) 1124 subjects (SSC) 1835 subjects (AGRE) |
CNV analysis | More significant CNVs that could infer ASD risk were identified using combined large clinical datasets of neurodevelopmental disorders than with ASD cohorts alone |
| [323] | SSC | Lymphoblasts | 5451 subjects | Association study | No association was found for heterozygous mutations in CNTNAP2 and contribution to ASD risk |
| [324] | SSC | Blood and lymphoblastoid cell lines | 593 families | Method description | A novel method was used to detect de novo and transmitted insert-deletions(Intel’s) in exomic data |
| [325] | SSC | Blood | 1315 subjects (total) 145 subjects (SSC) |
CNV analysis | Duplication CNVs enriched in negative regulation categories, deletion CNVs enriched in positive regulation categories. Highly connected genes in network enriched in patients with a single gene CNV change |
| [65] | SSC | Blood | 677 subjects (SSC) | WES | De novo mutations paternal in origin (4:1) and positive correlation with age. Recurrent mutations in genes CDH8 and NTNG1. |
| [64] | SSC | Blood | 20 families (total) 19 families(SSC) |
WES | 21 de novo mutations identified. 11 of which found to be protein altering. Mutations identified in FOXP1, GRIN2B, SCN1A, LAMC3 and CNTNAP2. |
| [87] | SSC | Blood | 2246 subjects (SSC) | WES | 27 de novo events found in 16 genes, 59% predicted to truncate proteins. further support for genotype-phenotype relationship in CDH8 and DYRKA1 |
| [326] | SSC | Blood | 19 subjects (total) 4 subjects (SSC) |
Genotype-phenotype | Overexpression/increased dosage of MECP2 related with core features of ASD |
| [133] | AGRE SSC |
Data taken from [327] | 8816 subjects (total) 737 subjects (SSC) 4449 (AGRE) |
Replication study | Findings could not be replicated from Skafidas paper |
| [328] | SSC DNBS |
Genomic data | 38000 subjects (total) 4358 subjects (SSC) 19142 subjects (DNBS) |
General population study | Genetic influences on ASD risk found to influence typical variation in social and communication ability in the general population |
| [67] | SSC | Blood | 2256 subjects | De novo and familial influences | Familial influences were more significant in cases of high-functioning ASD conditions. |
| [327] | SSC | Lymphoblasts | 1 subject | Clinical report | De novo microdeletion in chromosome 3q29 associated in person with ASD, childhood psychosis and intellectual disability |
| [68] | SSC | Genomic data | 1024 families | De novo mutation analysis | Significant role for loss of function mutations in ASD cases. |
| [329] | AGRE SSC |
Blood | 8816 subjects (total) 737 subjects (SSC) 4449 subjects (AGRE) |
Predictive testing | Diagnostic classifier containing 237 SNPs and 146 genes |
| [330] | SSC AGRE |
Blood | 975 subjects (total) 392 subjects (SSC) 585 subjects (AGRE) |
Genotype-phenotype study | NPAS1 found to repress generation of specific subtypes of cortical interneurons |
| [85] | SSC | Blood | 53 families | Whole genome sequencing | Enrichment of disruptive mutations in putative regulatory regions in ASD patients |
| [71] | SSC | Blood | 9231 subjects | Genotype-phenotype study | Disrupting mutations in DYRK1A were linked to a subset of 15 patients with a syndromic form of ASD/ID. |
| [331] | SSC | Blood | 903 families | WES | Enrichment of non-synonymous and potentially pathogenic mutations in mitochondrial DNA in ASD patients compared to controls. Transmission of potential pathogenic mutations differed between mother-ASD pairs and mother-sibling pairs |
| [332] | SSC | Lymphoblasts | 1 family | Mutation analysis | PKA found to be an upstream regulator of UBE3A, where mutation in phosphorylation site results in hyperactivity of UBE3A |
| [333] | SSC | Blood | 686 subjects + 612 families (SSC) |
WES | Bi-allelic mutations found in genes enriched in inherited ASD cases (AMT, PEX7, SYNE1, VPS13B, PAH, POMGNT1) |
| [333] | SSC | Blood | 928 subjects | WES | Strong evidence that de novo mutations are associated with ASD |
| [69] | SSC | Blood, lymphoblasts and saliva | 1174 families | CNV analysis | Significant associations found between ASD and de novo duplications of chromosome 7q11.23. de novo CNVs identified in 5 other regions, including 16p13.2 |
| [334] | SSC | Blood and lymphoblasts | 2591 families | CNV analysis | De novo CNVs associated with ASD. 6 loci and 65 genes identified, many targeting the chromatin or synapse |
| [335] | SSC | Genomic data | 2337 families | Transmission disequilibrium | Excess of truncating inherited mutations associated with ASD. RIMS1, CUL7, LTZR1 identified as candidate genes |
| [336] | SSC | Genomic data | 411 families | Transmission disequilibrium | Affected ASD patients inherited more CNVs than their unaffected siblings, and these CNVs of ASD patients affected more genes. Enrichment of brain-specific genes in inherited CNVs amongst ASD patients |
| [312] | SSC | Genomic data | 10,942 subjects (total) 4942 subjects (SSC) |
Biased transmission study | Frequent biased transmission of disruptive mutations to Low IQ ASD patients. Low and high IQ subjects can be distinguished by mutational load. |
Study numbers listed as families or subjects wherever applicable