Table 2.
Overview of studies using the AGRE collection
| 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 |
Study numbers listed as families or subjects wherever applicable