Background
Autism bio-collections
Methods and search criteria
Inclusion criteria
Exclusion criteria
Name | Founded | Location | Type of sample collected and stored | Website/source paper |
---|---|---|---|---|
Autism Genetic Resource Exchange (AGRE) | 1997 | USA | Blood and immortalised cell lines | AGRE, www.agre.org
|
Simons Simplex Collection (SSC) | 2010 | USA | Blood and immortalised cell lines | |
Danish Newborn Screening Bio-collection | 1980’s | Denmark | Dried blood spot samples | |
Autism Tissue Program | 1998 | USA | Post-mortem brain tissue | |
Autism Spectrum Stem cell Resource | 2014 | USA | Skin fibroblasts, blood, induced pluripotent stem cells, neural stem cells, neuronal cells, glial cells | [25] |
The Autism Simplex Collection | 2010 | USA and Europe | Blood | [97] |
Autism Inpatient Collection | 2014 | USA | Blood and lymphoblasts | [24] |
Results
Autism Genetic Resource Exchange (AGRE)
Reference | Bio-collection | Samples | Number | Study | Findings |
---|---|---|---|---|---|
[35] | AGRE | Genomic data (AGRE), brain tissue (mouse) | 4327 samples (AGRE) 8789 samples (total) | Genotype-phenotype study |
HMGN1 found to be a negative regulator of MECP2 expression. Dysregulation alters behaviour in mice, and AGRE collection contains genotypes linked to altered expression |
[180] | AGRE | Blood | 152 subjects | Quantitative trait analysis | Chromosome region 7q found to be a risk region for Autism Symptoms |
[181] | AGRE | Lymphoblasts | 1438 subjects | Association study |
CNTNAP2 identified as an ASD susceptibility gene |
[182] | AGRE | Blood | 1794 subjects | Linkage analysis | Chromosome 7q35 may harbour a gene that could contribute to variability in spoken language |
[183] | AGRE | Genomic data | 455 subjects | Pedigree study | Association found with chromosome X region Xp22.11-P21.2, where gene IL1RAPL1 is located and also implicated in ASD |
[184] | AGRE | Blood and lymphoblasts | 252 families | Gene expression analysis and association |
ROBO1-4 found to be associated with ASD. Low expression levels of ROBO1-2 found in ASD patients |
[185] | AGRE | Blood and lymphoblasts | 3211 subjects | Gene association study | Analysis of SNP polymorphisms in PCDHA suggest it as a potential candidate gene for ASD |
[186] | AGRE and ATP | Lymphoblasts and brain tissue | 3211 subjects (AGRE) 21 subjects (ATP) | Gene association study |
ZNF804A found to be associated with ASD and verbal deficits, where knockdown of this gene reduced expression of SNAP25, and both are reduced in the anterior cingulate gyrus in ASD brains. |
[187] | AGRE | Blood and lymphoblasts | 72 families | Association study | Common variant found in CNTNAP2 that is linked to ASD susceptibility |
[43] | AGRE | Blood | 470 families (total) 224(AGRE) | Association study |
GABRB3 and GABRG3 found to be associated with ASD |
[188] | AGRE | Blood and lymphoblasts | 975 subjects | CNV analysis | Analysis of 15q13.1-3 region revealed APBA2 as an ASD candidate gene |
[189] | AGRE | Blood and lymphoblasts | 1577 subjects (total) 1526 subjects (AGRE) | CNV analysis |
CNTNAP2 detected in ASD patients suggested to have a contribution to the disorder |
[74] | AGRE | Lymphoblasts | 6 subjects | Proof of principle | 48 genes showed differential expression between patients and controls. Many genes involved in signalling, focal adhesion and metabolism |
[190] | AGRE | Lymphoblasts | 18 subjects* (controls provided by AGRE) | Profiling study | Altered levels of UBE3A (1.5–2 fold increase) expression found in ASD patients with 15q11-14 duplications. APP and SUMO found to be decreased, and are involved in apoptosis |
[40] | AGRE | Blood and lymphoblasts | 334 families | Reanalysis of data set using different analysis method | Association found in chromosome 1, which was previously overlooked. Further evidence that 17q11 is associated with ASD |
[191] | AGRE | Genomic data | 12 families | Method paper | Description of parent of origin method to detect mosaic chromosomal abnormalities. |
[192] | AGRE | Blood and lymphoblasts | 518 families | Replication study and functional study | The gene EN2 suggested to act as ASD susceptibility locus, and mutations could alter brain development |
[41] | AGRE | Blood and lymphoblasts | 389 families (AGRE) 518 families (total) | Association study | Haplotypes found in ASD families found to affect regulation of EN2 gene expression |
[75] | AGRE | Blood and lymphoblasts | 954 subjects | Gene-gene interaction study | Glutathione pathway is implicated in autism |
[28] | AGRE | Blood and lymphoblasts | 6056 subjects (TOTAL) 4444 subjects (AGRE) | GWAS |
UBE3A, NRXN1, BZRAP, and MDGA2 found to have disruptive CNVs amongst ASD patients, some only occurring once amongst patients |
[83] | AGRE | Genomic data | 830 subjects | Methods paper | Use of disease symptoms improves detection of linkage in genetic data. Useful when heterogeneity is involved |
[38] | AGRE | Blood | 18 subjects | Genotype-phenotype study | 3 out of 18 patients with ASD and macrocephaly had mutations in PTEN gene. Considered as ASD gene to be explored |
[39] | AGRE | Blood and lymphoblasts | 88 subjects (total) 39 subjects (AGRE) | Mutation screening | De novo missense mutation found in one patient with ASD and macrocephaly. |
[193] | AGRE | Blood and lymphoblasts | 95 families | Gene linkage study | Chromosome region 2q suggested to contain an autism susceptibility gene |
[53] | AGRE | Blood | 88 families(total) 62 families (AGRE) | Linkage analysis |
GABRB3 polymorphism found to be associated with ASD |
[194] | AGRE | Blood | 115 families | Linkage analysis | Analysis carried out for a ASD family subset with obsessive compulsive behaviours (n = 35) found evidence of linkage to chromosome 1 and further evidence on chromosome 6 and 19 |
[82] | AGRE | Blood and lymphoblasts | 279 subjects | Method paper | Multiplex ligation-dependent probe amplification shown to be effective at detecting microduplications and deletions |
[50] | AGRE | Genomic data | 748 subjects | Association study |
MET variants associated with social and communication phenotypes amongst people ASD |
[49] | AGRE | Blood and lymphoblasts | 2712 subjects (total) 631 subjects (AGRE) | Association study | Multiple genes implicated in the MET pathway with ASD, such as PLAUR and SERPINE1
|
[48] | AGRE | Blood | 743 families (total) 283(AGRE) | Association study |
MET promoter variant that decreases expression found to be associated with ASD |
[195] | AGRE | Blood and lymphoblasts | 109 subjects | Replication study | Independent sample from the same cohort showed same linkage association to chromosome region 17q21 |
[196] | AGRE | Blood | 480 families | Genetic score study | 3 risk SNPs (ATP2B2, PITX1, HOXA1) had high reproducibility in males, 2 in females (MARK1, ITGB3), and 3 across both genders (CTNAP2, JARID2, EN2). |
[197] | AGRE | Blood | 381 subjects | Association study | Association between ASD in males and ATP2B2
|
[198] | AGRE | Blood | 2569 subjects | Functional genomics study | Combining functional genomics and statistical analysis helped identify common variants in ASD |
[199] | AGRE | Blood | 2837 subjects | Association study | Rare haplotype affecting promoter of DLX1 found to be associated with ASD. No common variants found for DLX genes and GAD1
|
[200] | AGRE | Blood | 2261 subjects | GWAS | The chromosome regions Xp22.33/Yp11.31 suggested to harbour male specific variants for ASD |
[201] | AGRE | Blood | 1132 subjects | QTL analysis | Chromosome regions 16p12-13 and 8q23-24 linked to harbour genes contributing to deficits in non-verbal communication in autistic patients |
[202] | AGRE | Blood | 993 subjects | Association study | Glu27 allele of ADRB2 gene suggested to confer increased risk of autism, with pregnancy related stressors having an increased effect |
[203] | AGRE | Blood and brain tissue | 90 subjects | Gene identification | Identification of the gene CORTBP2 from autism candidate region 7q31 |
[54] | AGRE | Blood | 611 families | Association study | Reinforced evidence that GABRA4 and GABRB1 are implicated in ASD. Other ethnic groups found to have SNPs in these genes |
[204] | AGRE | Blood | 228 families (total) 38 (AGRE) | Association study |
HOXG1 polymorphism A218G found to be associated in increased head circumference amongst ASD patients |
[205] | AGRE | Genomic data | 2165 subjects + 1165 families (total) 2165 subjects (AGRE) | GWAS | Associations found in the following genes with ASD and linked co-morbidities; KCND2, NOS2A and NELL1
|
[206] | AGRE | DNA | 37 twin sets (total) 15 twin sets (AGRE) | Association study | Terbutaline exposure for two or more weeks associated with increased concordance for ASD. 2 polymorphisms for ADRB2 associated with ASD |
[207] | AGRE | Blood | 284 families (total) 38 families (AGRE) | Linkage/association study | Variants of PON1 found to be associated with ASD families in North America, but not in Italian families |
[208] | AGRE | Blood | 38 subjects | CNV study | Microdeletions and duplications on chromosome regions 3p26.3, 6q24, 22q11.2, 4q34.2 and 1q24 linked to ASD with physical anomalies. Genes STXBP5 and LRRN1 identified as candidate genes |
[209] | AGRE SSC | Genomic data | 2294 subjects (SSC) 579 subjects (AGRE) 35663 | CNV analysis | Exploration of evolution of human specific SRGAP2 genes. Rare duplications observed in SSC cohort for SRGAP2C. |
[210] | AGRE | Genomic data from [211] | 121 families | QTL-analysis | 2 loci were identified in chromosomes 11 and 17 associated with social responsiveness in ASD families |
[81] | AGRE | Blood | 411 families (total) 371 families (AGRE) | Method paper | Detection of amplicons using mismatch repair. More amplicon variants were found in patients compared to controls |
[212] | AGRE | Blood | 66 subjects | Metabolite analysis | ASD families have lower levels of unprocessed Reelin protein in blood than controls |
[213] | AGRE | Blood | 90 subjects | Gene characterisation |
CADPS and CADPS2 characterised and cloned. Found to be activators of protein secretion. No disease specific variants found amongst ASD patients |
[214] | AGRE | Genomic data | 1146 subjects | Linkage analysis | Linkage peaks found for language—speech phenotypes consistent with potential motor speed disorder in following chromosome regions; 1q24.2, 3q25.31, 4q22.3, 5p12, 5q33.1, 17p12, 17q11.2, 17q22, 4p15.2 and 21q22.2. multiple candidate genes were also identified |
[215] | AGRE | Blood | 2140 subjects | Linkage analysis | Parental origin effect significantly linked to chromosomes 4, 15 and 20 |
[42] | AGRE | Blood | 167 families | Association study |
EN2 found to be associated with ASD susceptibly |
[216] | AGRE | Blood and lymphoblasts | 537 subjects (total) 34 subjects (AGRE) | CNV analysis | Proposal that increased CNV load, particularly duplication of base pairs, predisposes to ASD. Negative correlation found with CNV load and social and communication skills. Applied to both common and rare CNVs |
[73] | AGRE | Blood and lymphoblasts | 4714 subjects (total) 1336 subjects (AGRE) | CNV analysis | Genes involved in Neuronal adhesion (NLGN1, ASTN2) and ubiquitin pathways (UBE3, PARK2, RFWD2, FBXO40) were found in ASD patients. Further evidence of NRXN1 and CNTN4 involved with ASD. |
[217] | AGRE | Blood | 147 subjects | Genotype phenotype | Suggested relationship between polymorphism MTFR 677C → T and autism-related behaviours |
[218] | AGRE | Blood and lymphoblasts | 693 subjects (AGRE) 5878 subjects (total) | CNV analysis | Microduplications and microdeletions in chromosome 16p11.2 associated with psychiatric disorders; duplications associated with schizophrenia, bipolar disorder and ASD, and deletions with ASD and other neurodevelopmental disorders |
[219] | AGRE | Blood | 219 subjects | Variant analysis |
DLX1/2 and DLX5/6 gene analysis may not contribute to ASD but functional analysis of variants still worth investigation |
[36] | AGRE | Blood | 1410 (total) 401 (AGRE) | Association study | No association found for a sequence variant in mental retardation found in exon 1 of MECP gene in autism cohort |
[220] | AGRE | Blood and lymphoblasts | 112 families(total) 79 families (AGRE) | Association study | A haplotype for DRD1 is found to be associated with ASD risk amongst males |
[221] | AGRE | Data from [222] | 551 subjects (AGRE) | SNP analysis | Analysis of SNPs revealed variants of CD38 associated with ASD. Variants of CD38 linked to control of OXT secretion. |
[223] | AGRE | Lymphoblastoid cell | 14 subjects | Gene expression analysis | First study to show differential expression between lymphoblastoid cell lines. Genes affected implicated in cell death and development, nervous system development and immune development and function |
[224] | AGRE | Lymphoblasts | 116 subjects | Gene expression analysis | Patients with severe ASD showed altered expression of genes involved in Circadian rhythm. 20 novel genes found putative non-coding regions associated with androgen sensitivity |
[225] | AGRE | Genomic data | 1295 families (total) 696 families (AGRE) | GWAS | Noise reduction filter for GWAS leads to list of 830 candidate genes, where they impact dendrite and axon outgrowth and guidance |
[29] | AGRE ATP | Blood and brain | 133 sib pairs (total) 77 Sib pairs (AGRE) 17 brain tissue (ATP) | Ogliogenic hypothesis study | Evidence of epigenetic and genetic factors possibly contributing to ASD and UBE3 having a possible role in ASD |
[179] | AGRE | Blood and lymphoblasts | 192 subjects (AGRE) 483 subjects (total) | Association study | Disruptions in NRXN1 gene found to be associated with ASD |
[226] | AGRE | Genomic data | 476 subjects (total) 290 subjects (AGRE) | Association study | Suggestive association of parent and maternal origin effect on SLC6A4 promoter variant and ASD. Further testing required on biological model or larger cohort |
[26] | AGRE | Blood and lymphoblasts | 1549 subjects 410 subjects (AGRE) | Mutation screening | Recurrent microdeletions in chromosome region 16p11.2 were observed in ASD patients and not in controls |
[227] | AGRE | Blood and lymphoblasts | 974 subjects (total) 512 subjects (AGRE) | Mutation screening |
RIMS3 identified as a possible ASD susceptibility gene |
[228] | AGRE | Blood | 33 families (AGRE) 49 families (total) | Association study | Association found for HLA-DR4 gene in higher frequency in geographically defined subtype, but not in controls or AGRE sample |
[229] | AGRE | Blood | 508 families (total) 139 families (AGRE) | Association study | Analysis of 2p15-16.1 microdeletions region identified two candidate genes; XPO1 and OXT1
|
[230] | AGRE | Blood and lymphoblasts | 407 families (total) 138 families | Association analysis | Polymorphisms found in or near DLX1 and DLX2 found to be associated with ASD |
[231] | AGRE | Blood and lymphoblasts | 512 families (total) 138 families (AGRE) | Association study | Association found between ASD and MTHFR gene in simplex families but not in multiplex families |
[37] | AGRE | Blood and lymphoblasts | 219 families (total) 98 families (AGRE) | Association study | Polymorphisms in MECP2 found to be associated with ASD |
[232] | AGRE | Genomic data | 990 families | Association study | 2 genes found to be associated with ASD; RYR2 and UPP2
|
[233] | AGRE | Genomic data | 2194 families (total) 543 families (AGRE) | Association study | Association found between the calcium channel genes (CACNA1L, CACNA1C and CACNA1) with ASD |
[32] | AGRE | Blood | 470 families (total) 224 families (AGRE) | Gene association studies |
GABRA4 and GABRB1 found to be associated with ASD |
[234] | AGRE | Genomic data | 680 families (AGRE) 1167 families (total) | GWAS | Identification of a common novel risk locus as chromosome region 5p14.1. Common and rare variants identified. AGRE used as validation dataset |
[75] | AGRE | Lymphoblasts | 12 subjects | Cell necrosis | Cells from autistic patients were more susceptible to oxidative and nitrosative stress |
[235] | AGRE | Blood and lymphoblasts | 1142 subjects (total) 139 families (AGRE) | Association study |
GTF2i found to be associated with ASD |
[236] | AGRE | Blood and lymphoblasts | 207 families | CNV analysis | Translocation between short arms of chromosome 16 and 15 reported in 1 female patient. Nominal association of A2BP1/FOX1 observed in ASD cohort. |
[237] | AGRE | Serum | 21 human subjects 13 rhesus monkeys | Exposure study | Monkeys exposed to antibodies from human mothers of autistic children displayed stereotypies and hyperactive behaviour. Autoimmune component suggested to contribute to ASD |
[238] | AGRE ATP | Blood, lymphoblasts and brain tissue | 276 families (AGRE) 17 subjects (ATP) | Association study |
MARK1 gene found to be associated with ASD. Overexpression of gene also found in prefrontal cortex (BA46) but not cerebellum in human post-mortem tissue. Mouse model showed abnormalities in dendrites. |
[55] | AGRE | Blood | 123 families (total) 75 Families (AGRE) | Linkage disequilibrium study | Nominal evidence found for ASD risk alleles in GABAa Receptor subunits |
[52] | AGRE | Blood | 137 families (total) 80 families (AGRE) | Linkage and association study |
SLC6A4 found not to be associated to rigid-compulsive subset of ASD patients. |
[239] | AGRE | Blood | 158 families (total) | Linkage analysis | Increased support that chromosome regions 19p13 and 17q11.2 harbour ASD susceptibility loci |
[240] | AGRE | Blood and lymphoblasts | 1336 subjects (AGRE) 1509 subjects (total) | CNV analysis | Large-scale survey of 15q24 microdeletion syndrome identifies atypical deletion that narrows critical region and (776 kb versus 1.75mb) and number of genes (15 versus 38) sequencing of genes recommended |
[241] | AGRE | Genomic data | 4278 subjects (total) 1518 subjects (AGRE) | Transmission disequilibrium testing | AGRE dataset found to have a genome wide signals at chromosome region 10q26.13 in both sexes and paternal signals in 6p21.1 |
[30] | AGRE | Blood and lymphoblasts | 2886 subjects (total) 1441 subjects (AGRE) | CNV analysis | Microdeletions and duplications at chromosome region 15q13.2q13.3 found to be associated with ASD symptoms and other psychiatric disorders |
[242] | AGRE | Blood and Lymphoblasts | 34 subjects | Linkage analysis study | Chromosomes 7q and 21q are associated with a subset of ASD patients with developmental regression |
[222] | AGRE | Blood and brain tissue | 1221 subjects (total) 263 subjects (AGRE) | Association study | Two genetic variants of CD38 found to be associated with ASD |
[243] | Blood | 233 subjects | Association study | HOXA1 A218G alleles found to significantly influence head growth rates. | |
[244] | AGRE | Blood | 196 families | Association study | Association not found between SNPs in DLX6 and PLCO on chromosome 7q21-22 and ASD |
[245] | AGRE | Blood | 196 families | Association study | Presence of a susceptibility mutation found in TDO2 or nearby gene |
[246] | AGRE | Blood and lymphoblasts | 249 families | Association study | Elevated levels of STX1A found to be associated with ASD |
[47] | AGRE and ATP | Lymphoblasts | 14 subjects (AGRE) 84 subjects (ATP) | Methylation study | Different methylation patterns found for genes involved in cell death/survival, neurodevelopment and gene transcription. Decreased expression of RORA and BCL2 was found in brain samples of ASD patients |
[247] | AGRE | Blood and lymphoblasts | 110 subjects | Genetic association study | Association found between PER1 and NPAS2 and ASD |
[248] | AGRE | Blood and lymphoblasts | 104 families | Genetic association study |
BDNF associated with ASD; significantly higher expression in ASD subjects |
[249] | AGRE | Blood and lymphoblasts | 13,205 subjects (total) 80 subjects (AGRE) | CNV analysis | Disruption of the PTCHD1 locus on Xp22.11 identified in families with ASD and in families with Intellectual disability. Novel CNVs identified in DPYD and DPP6. |
[80] | AGRE and ATP | Lymphoblasts and brain tissue | 13 subjects (AGRE) 3 subjects (ATP) | Genotype-phenotype study | Increased dosage of the gene CYFIP1 results in altered cellular and dendritic morphology and dysregulates mTOR pathway in ASD patients with duplications in 15q11-13 |
[250] | AGRE | Blood and lymphoblasts | 95 subjects (AGRE) 134 subjects (total) | Genomic and molecular study | No coding mutations or parental-specific expression found in ASD and Gilles de la tourettes syndrome (GTS) in the gene IMMP2L. Gene should not be written out as factor for both conditions |
[251] | AGRE | Blood and lymphoblasts | 283 families | Linkage mapping study |
PRKCB1 shown to be associated with ASD |
[252] | AGRE | Blood and lymphoblasts | 1086 subjects | Candidate gene study |
PITX1 shown to be associated with ASD |
[253] | AGRE | Blood | 406 families (total) 99 Families (AGRE) | Association and linkage disequilibrium study |
GAD1 SNPs found not to be associated with ASD |
[254] | AGRE | Blood | 322 families (total) 86 families (AGRE) | Association study | No association found with APOE gene and ASD. |
[255] | AGRE | Genomic data | 4530 subjects | Association study | Immune function genes CD99L2, JARID2 and TPO show association with ASD |
[256] | AGRE | Blood and lymphoblasts | 334 families | Association study | Analysis of 2q24-q33 region found following genes associated with ASD; SLC25A12, STK39 and ITGA4
|
[257] | AGRE | Blood and lymphoblasts | 411 families (total) 371 families (AGRE) | Linkage analysis | Linkage analysis of SNPs suggests SLC25A12 to be associated with ASD |
[258] | AGRE | Blood and lymphoblasts | 352 families | Association study | No association found between polymorphisms in TPH1 and TPH2 and ASD susceptibility or endophenotypes |
[259] | AGRE | Blood and lymphoblasts | 352 families (total) 295 families (AGRE) | Association study | No association found between SLC6A4 variants and susceptibility to ASD |
[260] | AGRE | Blood and lymphoblasts | 1011 subjects | Association study |
AHI1, a gene associated with Joubert Syndrome, is also implicated in ASD |
[261] | AGRE | Genomic data | 2883 individuals | Methods paper | Tool that provides visualisation of SNP data |
[262] | AGRE | Serum | 34 subjects | Metabolite study | ASD patients had lower levels of the enzyme AAT in serum compared to controls. Difference is much more significant in ASD patients with regressive onset |
[263] | AGRE | Blood and lymphoblasts | 486 subjects (total) 252 subjects (AGRE) | Genotype-phenotype study | Mice with CADPS2 knockout display autistic-like behaviour and cellular features. Analysis of human Cadps2 mRNA revealed aberrant splicing that resulted in some patients lacking exon 3 of the transcribed gene |
[264] | AGRE | Blood and genomic data | 860 subjects (total) 468 subjects (AGRE) | GWAS | Regions in 5q21.1 and 15q22.1-q22.2 found to have most significant association in combined data for Asperger. 8 regions overlap with ASD linkage areas, and 3 overlapped with a Finnish cohort |
[79] | AGRE | Lymphoblasts | 14 subjects | MicroRNA analysis | Dysregulation of MicroRNA expression contributes to gene expression in ASD. Gene targets ID3 and PLK2 were validated by knockdown and overexpression assays |
[265] | AGRE | Genomic data | 289 families | Method paper | SNPs involved in three-way epistatic interactions found and all located in gene GLRX3 |
[58] | AGRE | Blood and lymphoblasts | 264 families | CNV analysis | De novo CNVs were found to be strongly associated with Autism |
[266] | AGRE | Blood and lymphoblasts | 248 subjects (total) 146 subjects (AGRE) | Association study | Results suggestive that a y-chromosome haplotype effect is associated with ASD |
[267] | AGRE | Blood and lymphoblasts | 196 families | Transmission analysis | Polymorphisms in INPP1, PIK3G and TSC2 found to have linkage disequilibrium in ASD subjects |
[268] | AGRE | Blood and lymphoblasts | 196 families | Transmission analysis | Suggestive evidence that GRM8 is a susceptibility gene in ASD |
[269] | AGRE | Blood and lymphoblasts | 196 families | Association study | Suggestive but tentative evidence for MTF1 and SLC11A3 as ASD suspectability genes |
[270] | AGRE | Blood and lymphoblasts | 10 subjects | Whole genome sequencing | 59 candidate genes suggested to be associated with ASD susceptibility, with ANK3 being the top result. 33 non-coding variants were also identified. |
[271] | AGRE | Genomic data [73] | 1336 subjects | Method paper | CNV analysis method that uses both B-allele frequency and log R ratio to find CNVs. Found all 21 validated short duplications in AGRE dataset. Analysis is much faster. |
[272] | AGRE | Blood and lymphoblasts | Data taken from Ramoz, 2004 | Association study | Suggestive association found for ASD-related routines and rituals with a polymorphism in SLC25A12
|
[273] | AGRE | Blood and lymphoblasts | 144 subjects | Sequencing study | 7 rare variants found in NLGN3 and NLGN4X. UTR found not to be significant. 2 intronic variants suggested to influence regulation of genes. Limited by throughput and cost |
[274] | AGRE | Blood | 351 families | Association study | Nominal significance found for 15 genes, top 3 being MYO1D, ACCN1 and LASP1 suggested for further study |
[275] | AGRE | Genomic data | 148 families | Linkage analysis | Male-specific linkage mapped to chromosome 17q11. Evidence of sex specific risk alleles in ASD |
[56] | AGRE | Lymphoblasts | 284 subjects | Association study |
CACNAG identified as a candidate gene for ASD |
[276] | AGRE | Lymphoblasts | 267 subjects (AGRE) | Linkage and association study |
SLC6A4 shown to contribute to ASD susceptibility |
[78] | AGRE | Lymphoblasts | 12 subjects | MicroRNA study | Lymphoblastoid cell lines from ASD patients can be used to assess microRNAs in ASD. Dysregulated MicroRNAs found to target genes linked to ASD |
[277] | AGRE | Blood samples | 100 subjects | Cholesterol metabolism | 20% of the samples have shown hypercholestolemia, indicating that cholesterol metabolism could be perturbed in ASD |
[278] | AGRE | Genomic DNA | 756 subjects | Association study |
EGF found to have significant association with ASD |
[279] | AGRE and ATP | Data mining (AGRE) brain tissue (ATP) and blood | 83 subjects | Linkage study | 3p26.1, 3p26.3, 3q25-27 and 5p15 enriched for differentially expressed genes in blood and brain tissue. CNTN4, CADPS2, SUMF1, SLC9A9 and NTRK3 implicated in ASD and even more genes involved in neurological disorders that are co-morbid with ASD |
[280] | AGRE | Blood | 97 families | Expression profile analysis |
RAY1/ST7 locus found to contain a multi-transcript system. Screening of ASD patients found rare variants not present in controls |
[281] | AGRE | Blood and lymphoblasts | 196 families (total) 95 families (AGRE) | Mutation screening | No mutations found in coding regions of X-chromosomal NLGN genes. |
[282] | AGRE | Blood and lymphoblasts | 136 families (total) 96 families (AGRE) | Association study | High association of FMR1 gene variant found amongst east Asian individuals, but not when whole sample was analysed, stratification confounded result |
[283] | AGRE | Lymphoblasts | 11 subjects | Neurotoxicity | Both ASD patients and controls showed upregulation of heat shock proteins when expressed to thimerosal |
[33] | AGRE | Blood and lymphoblasts | 3101 subjects (AGRE) 10796 subjects (total) | GWAS | Genome-wide SNPs found in CDH10 and CDH9 found to be associated with ASD |
[284] | AGRE ATP | Blood, lymphoblasts and brain tissue | 1031 families (AGRE) 3104 families (total) 30 subjects (ATP) | GWAS | Analysis found association in chromosome region 5p15, where genes SEMA5A and TASR2 are located. Analysis of brain tissue showed reduced expression of SEMA5A in ASD subjects |
[27] | AGRE | Lymphoblasts | 5675 subjects (AGRE) | Association study | Micro deletion found in chromosome 16p11.2. amongst AGRE, Boston Children’s Hospital and Icelandic population data sets |
[57] | AGRE | Blood | 229 families | Association study | Sodium channel genes SCN1A1-3 contained SNPs of interest amongst ASD families for future studies |
[285] | AGRE | Blood | 564 families (total) 327 families (AGRE) genetic analysis only 261 subjects (serotonin analysis) | Association study |
ITGB3 genetic variation found to be associated with serotonin blood levels and ASD susceptibility |
[286] | AGRE | Genomic data | 5328 subjects | Recurrence rate study | Significant difference in recurrence rates between male only families and female carriers in regard to ASD. Female protective effect suggested to be at work in high genetic-risk families involving female carriers. Shorter interbirth intervals correlated to ASD risk. |
[287] | AGRE | Blood lymphoblasts | 1587 subjects | Linkage analysis | Replication of linkage on 20p13. Linkage found for chromosomes 6q27, 8q13.2, 1p31.3, 8p21.2 and v8p12 |
[288] | AGRE | Lymphoblasts | 75 subjects (total) 50 subjects (AGRE) | Gene characterisation | Gene characterised and assessed for mutation amongst ASD patients. No concrete association found |
[289] | AGRE | Genomic data | 487 families | Method paper | Pathways of interest analysed using GWAS SNP data. 5 pathways shown to be of significance in regards to ASD |
[290] | AGRE | Blood and lymphoblasts | 383 subjects | Loci analysis | AGRE and Finnish ASD dataset both showed strong association with 3p24-26 locus containing the gene OXTR
|
[211] | AGRE | Blood and lymphoblasts | 833 families | Genome-wide screen | Evidence of linkage to ASD found on chromosomes 17, 5, 11, 4 and 8, of which 17 having the highest association score in the group |
[291] | AGRE | Blood and lymphoblasts | 110 families | Genome-wide linkage analysis | Nominal evidence for linkage found in chromosomes 2–4,8, 10–12,15-16,18 and 20. significant linkage found for chromosomes 5 and 8 after reanalysis |
[292] | AGRE | Blood and lymphoblasts | 389 families | Association study | No evidence found that RH -ABO foetal-maternal incompatibility is associated with ASD |
[46] | AGRE | Blood | 126 families (total) 81 families (AGRE) | Association study |
RELN alleles with large CGG repeats may play a role in aetiology of certain ASD cases |
[293] | AGRE | Blood and lymphoblasts | 165 subjects | Population genetics | Study suggested two groups: low risk families caused by spontaneous mutations, and high risk caused by female offspring that carry ASD-causing mutation that is passed onto their own offspring |
[294] | AGRE | Blood and lymphoblasts | 205 families | Gene association study | No association found between ASD and variant of the gene EN2
|
[295] | AGRE | Lymphoblasts | 20 subjects | Intracellular redox study | Inbalance of glutathione redox in cell lines derived from patients with ASD |
[76] | AGRE | Lymphoblasts | 86 subjects | Transmethylation/transsulfuration study | Cell lines derived from parents of ASD children showed abnormal transmethylation/transsulfuration metabolism and DNA hypomethylation |
Simons Simplex Collection (SSC)
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 | 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. |
Danish Newborn Screening (NBS) Biobank
The Autism Simplex Collection (TASC)
Autism Inpatient Collection (AIC)
Autism Tissue Program (ATP)/Autism BrainNet
Replication studies and pooling resources
Reference | Bio-collection | Samples | Number | Study | Findings |
---|---|---|---|---|---|
[136] | DNSB | DBSS | 1100 subjects | Chemokine analysis | Analysis of crude estimates showed decreased levels of RANTES. Adjusted estimates showed no significance amongst 3 chemokines studied (RANTES, MCP-1, MIP-1A). Cautious suggestion of altered immunity in neonatal period amongst ASD patients |
[96] | DNSB | DBSS | 1200 subjects | Cytokine analysis | Suggestive evidence of decreased levels of certain th-1 and th-2 like cytokines in newborns later diagnosed with ASD. |
[136] | DNSB | DBSS | 1029 subjects | Neurotropic factor analysis | Decreased level of neurotropic factors found in ASD patients during Neonatal period |
Reference | Bio-collection | Samples | Number | Study | Findings |
---|---|---|---|---|---|
[337] | ATP and AGRE | Brain tissue, blood and lymphoblasts | 18 subjects (ATP) 841 families (AGRE) 1029 families (total) | Gene expression and association analysis | Altered expression of mitochondrial genes in anterior cingulate gyrus, motor cortex and thalamus of ASD patients. Polymorphisms in MTX2, NEFL and SLC25A27 found to be associated with ASD. |
[338] | ATP | Brain tissue | 18 subjects | Gene expression analysis | Reduced expression of several genes related to electron transport in anterior cingulate gyrus, motor cortex and thalamus of ASD patients |
[339] | ATP | Brain tissue | 57 subjects | Functional genomic study | Analysis of CNVs showed differences of what pathways are altered between children and adults; cell number, cortical patterning and differentiation in the former, and signalling and repair pathways in the latter. Prefrontal cortex samples were used |
[106] | ATP | Brain tissue | 33 subjects | GWAS | Patients with ASD had more genes that were up- or down-regulated in an- individual specific manner when prefrontal cortex tissue was examined |
[340] | ATP | Brain tissue | 126 subjects (total) 42 subjects (ATP) | Sequencing study | Recurrent deleterious mutations found in ARID1B, SCN1A, SCN2A and SETD2. Higher proportion of mutations that are deleterious, protein-altering or cause loss-of-function in ASD patients compared to controls. Cortical and cerebellar tissue was used. |
[107] | ATP | Brain tissue | 25 subjects | Deep sequencing study | Altered adenosine to inosine editing found in cerebella tissue from ASD patients. Dysfunctional for of editing enzyme ADARB1 more frequently in ASD Cerebella |
[341] | ATP | Brain tissue | 28 subjects (ATP) 43 subjects (total) | Gene expression analysis | Signalling partners of FMRP and GRM5 (HOMER1, APP, RAC1, STEP) shown to have altered expression in the cerebellar vermis and superior frontal cortex in ASD patients compared to controls. |
[342] | ATP | Brain tissue | 19 subjects | mRNA analysis | Reduction of multiple GABA receptor subtypes (A6, B2, D, E, G2, T and P2) detected in cerebella vermis and superior frontal cortex ASD patients |
[343] | ATP | Brain tissue | 25 subjects | Assay study | Imbalance in isoforms of precursor BDNF protein found in fusiform gryrus of ASD patients |
[103] | ATP | Brain tissue | 18 subjects | Transcriptional and epigenetic association analysis | Downregulation of genes related to oxidative phosphorylation and protein translation. Associations were found between specific behaviour domains of ASD and gene expression modules related to myelination, immune response and purinergic signalling. Cerebral and Brodmann area 19 tissue was used |
[108] | ATP | Brain tissue | 16 subjects | Methylation study | Increased methylation was found for the gene OTXR in ASD patients in blood and DNA from the temporal cortex |
[104] | ATP | Brain tissue | 107 subjects | Transcriptome analysis | Dysregulated gene expression associated with glial cells shown to have negative correlation with gene expression relating to synaptic transmission in ASD patients when Brodmann areas 10, 19 and 44 were analysed |
[344] | ATP | Brain tissue | 32 subjects | Transcription analysis | RORA may have dimorphic effects on gene expression in certain areas of cortical tissue between genders, and deficiency appears to cause greater gene dysregulation amongst males in both mice and humans |
[345] | ATP | Brain tissue | 30 subjects | Transcription analysis |
RPP25 expression is decreased in the prefrontal cortex of ASD patients |
[116] | ATP | Brain tissue | 23 subjects | Alternate splicing analysis and discovery | A conserved group of microexons involved in modulation of interaction domains of proteins and neurogenesis is disrupted in patients with ASD |
[29] | ATP | Brain tissue | 17 subjects | Methylation study |
UBE3 implicated as a contributing gene to autism and Angelman syndrome |
[346] | ATP | Brain tissue | 20 subjects | Anti-sense RNA study | Discovery of anti-sense non-coding RNA that binds to moesin at 5p14.1 in ASD cerebral cortex tissue |
[109] | ATP | Brain tissue | 40 subjects | Methylation study | 4 differentially methylated regions; 3 in temporal cortex and 1 in cerebellum. 3/4 regions were again found in different samples and brain regions. |
[117] | ATP | Brain tissue and lymphoblasts | 36 subjects (total) | Transcription and alternative splicing study | Accelerated decrease of MS gene transcription across ageing found in ASD patient cerebral cortex samples |
[347] | ATP | Brain tissue | 73 subjects | Methylation study | Correlation found between reduced expression of MECP2 and increased methylation on the promoter region |
[110] | ATP | Brain tissue | 24 subjects | Methylation study | Hypomethylation of mir142 and upregulation of mi-RNAs targeting OXTR gene in prefrontal cortex of ASD brains |
[348] | ATP | Brain tissue | 24 subjects | Signal transduction study | Downregulation of PI3K-Akt genes observed in fusiform gyrus tissue of ASD patients. Similar effects noted in rat brain tissue exposed to valproic acid |
[349] | ATP | Brain tissue (ATP) neuronal cells | 6 subjects | CHiP study |
RORA found to regulate 2BP1, CYP19A1, HSD17B10, ITPR1,
NLGN1 and NTRK2 via transcription. Low levels of RORA causes dysregulation of these genes and associated pathways. Prefrontal cortex and cerebellum tissue was used. |
[350] | ATP | Brain tissue (ATP) | 153 families (other) 54 subjects (ATP) | Functional characterisation study | Variant of the HTR2A gene rs6311 in ASD patients has lower level of expression and contains extended 5′untranslated region. Speculation that this variant could be a risk factor in ASD. Frontopolar cortex tissue was used. |
[351] | ATP | Brain tissue | 28 subjects | Micro-RNA study | Difference in pattern of micro-RNA expression between ASD superior temporal gyrus samples and controls. Further evidence that Mir-320, Mir-132 and Mir-302 are involved in ASD. |
[113] | ATP | Brain tissue | 94 subjects (total) 51 subjects (ATP) | Acetylome study | Common acetylome signatures found amongst 68% of ASD cases in 5000 regulatory regions in the prefrontal and temporal cortex. Acetylome profiles were not affected by SNPs at these regulatory regions. |
[352] | ATP and AGRE | Brain tissue, blood and lymphoblasts | 21 subjects (ATP) 252 families (AGRE) | Association study | Variants of LMX1B show modest association with ASD. Analysis of mRNA from anterior cingulate gyrus is much lower in ASD patients compared to controls. |
[105] | ATP | Brain tissue | 36 subjects | Gene co-expression network analysis | Transcriptional and splicing dysfunction implicated in disorder. Enrichment for genes in glial, immune and neuronal modules. Gene A2BP1 linked to alterations in splicing. Studies based on using temporal cortex, frontal cortex and cerebellum |
[353] | ATP | Brain tissue | 28 subjects (total) 8 subjects (ATP) | Gene expression analysis | Genes expressed at higher levels in males enriched in upregulated genes in post-mortem neocortical tissue in ASD patients, including astrocyte and microglia markers |
[118] | ATP | Brain tissue (ATP) and placenta | 12 subjects (ATP) 64 subjects (total) | Vitamin B12 study | Reduced levels of B12 found in ASD, aged and Schizophrenic patients compared to controls. oxidative stress found in ASD and Schizophrenia patients. Frontal cortex tissue was used |
[114] | ATP | Brain tissue | 98 subjects | Methylation study | Altered methylation patterns discovered in SHANK3 gene in cerebella tissue of ASD patients |
[115] | ATP | Brain tissue | 20 subjects | Epigenetic study | Enrichment of 5-hmc in cerebella tissue may be associated with increased binding by MECP2 to RELN and GAD1 promotors |
Reference | Biobank | Sample type | Number | Study | Findings |
---|---|---|---|---|---|
[119] | SSC and AGRE | Blood and genomic data | 8044 subjects (AGRE) 4348 subjects (SSC) | Genome-wide survey on translational effects | Investigation of maternal genetic effects in ASD. Validation using other data sets (SSC and AGRE) did not reproduce similar results). |
[354] | SSC and AGRE | Genomic and clinical data | Subjects (AGRE) 941 1048 subjects (SSC) | Gene association study |
ATP2C2 and MRPL19 found to be associated with language impairment and dyslexia, respectively |
[122] | SSC and AGRE | Blood | AGRE–127 subjects SSC–75 subjects | Parallel sequencing study | Rare variants of the AFF2 gene found to associated with ASD susceptibility in males |
[355] | SSC and AGRE | Genomic data | 359 subjects (AGRE) SS–885 subjects | GWAS | Female protective effect in ASD is not mediated by a single genetic locus. |
[356] | AGRE and SSC | Genomic data | 13 subjects (AGRE) 3 subjects (SSC) | WES | Loss of CTNND2 function linked to severe ASD |
[86] | SSC and TASC | Blood and lymphoblasts | 15480 (total) 2475(SSC) 601(TASC) | WES | 107 genes implicated in ASD. These genes are responsible for synaptic formation, chromatin remodelling and transcriptional regulation |
[123] | SSC and AGRE | Blood and lymphoblasts, genomic and clinical data | 5657 subjects (total) 1555 subjects (AGRE) 872 subjects (SSC) | WES | Mutations in SHANK1, 2 and 3 accounts for 1 in 50 ASD cases. SHANK1 mutations linked to mild effects, SHANK2 for moderate and SHANK2 for severe. |
Stem cell research and autism spectrum stem cell resource
Discussion
Phenotypic and genotypic heterogeneity
Samples
Organization
Reference | Subject of paper |
---|---|
[357] | Introduces concept of adding value to stakeholders (patient donors/funders/research customers) and to find balance between aspects of sustainability (acceptability/efficiency/accomplishment) |
[358] | Feasibility of simplified consent form for biobanking. Result indicates simplified forms combined with supplemental information for further reading effective in minimising form length and complexity |
[359] | Review paper detailing best practice guidelines for sample collection and storage, management of data and infrastructure. In addition, ethical, legal and social issues are explored |
[360] | Paper discussing aspects of embryonic stem cell banking that can be applied to iPSCS |
[361] | Key issues relating to delivery and safety testing of iPSC stocks for use in research and therapy. Importance of international and national coordinated banking systems are also discussed |
[362] | Description of enclosed culture system for iPSCS and neural precursors for use in preclinical and basic research |