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Table 2 Overview of studies using the AGRE collection

From: Bio-collections in autism research

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

  1. Study numbers listed as families or subjects wherever applicable