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TriosKanner Syndrome, Disorders, Genomes, Disorder, autism, Kanner's Syndrome, Early Infantile Autism, Infantile Autism, Kanners Syndrome, Autistic, Autism, stage, Early Infantile, Infantile, whole genome, Early, susceptiblity to, developmental stage.<p>Family-based sampling design, where cases were classified using the Autism Diagnostic Interview-Revised (ADI-R) and Autism Diagnostic Observation Schedule (ADOS) instruments and those with known karyotypic abnormalities, fragile X mutations or other genetic disorders were excluded.</p>https://www.ncbi.nlm.nih.gov/projects/gap/cgi-bin/study.cgi?study_id=phs000267<p>The Autism Genome Project (AGP) Consortium represents more than 50 centres in North America and Europe. In an ongoing effort, the international AGP Consortium is collecting ASD families for ongoing genetic studies. The first phase of this initiative involved examining genetic linkage and chromosomal rearrangements in 1,168 families having at least two ASD individuals (PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/17322880" target="_blank">17322880</a>). In this second phase of the project, we collected more families and genotyped them to examine for Copy Number Variation (CNVs) and SNPs affecting risk for ASD.</p> <p>Affected subjects were grouped in three classes (strict, broad and spectrum ASD) based on proband diagnostic measures. To qualify for the strict class, affected individuals met criteria for autism on both primary instruments, the ADI-R and the ADOS. The broad class included individuals who met ADI-R criteria for autism and ADOS criteria for ASD, but not autism, or vice versa. ADI-R-based diagnostic classification of subjects as ASD followed criteria published by Risi et al. (PMID: <a href="http://www.ncbi.nlm.nih.gov/pubmed/16926617" target="_blank">16926617</a>). Specifically, individuals who almost met ADI criteria for autism were classified as ASD if (1) they met criteria on social and either communication or repetitive behavior domains; or (2) met criteria on social and within 2 points of criteria for communication, or met criteria on communication and within 2 points of social criteria, or within 1 point on both social and communication domains4. Finally, the spectrum class included all individuals who were classified as ASD on both the ADI-R and ADOS or who were not evaluated on one of the instruments but were diagnosed with autism on the other instrument. Subjects from all classifications (strict, broad, and spectrum) were included in the CNV analysis.</p> <p>Family-history reports were taken to inform on the family type. Multiplex (MPX) families had at least two individuals receiving validated ASDs diagnoses who were first to third degree relatives (for third degree, only considered cousins). This included families with affected dizygotic twins. Simplex (SPX) families had only one known individual with ASD in first to third (cousin) degree relatives. Families with only affected monozygotic twins were considered SPX. Unknown (UKN) families were any families that did not fall into the MPX or SPX criteria above. Given the international and multi-site nature of the project and range of chronological and mental age of the probands, a range of cognitive tests were administered, and standard scores were combined across tests to provide consolidated IQ estimates.</p>Funding Source - MH080647 - National Institutes of Health, Bethesda, MD, USAFunding Source - MH061009 - National Institutes of Health, Bethesda, MD, USAFunding Source - Core award 075491/Z/04 - Wellcome Trust, UKFunding Source - HD055782 - National Institutes of Health, Bethesda, MD, USAFunding Source - Rubicon 825.06.031 - Netherlands Organization for Scientific ResearchFunding Source - NS042165 - National Institutes of Health, Bethesda, MD, USAFunding Source - Convention 181 of 19.10.2001 - Italian Ministry of HealthFunding Source - HD055751 - National Institutes of Health, Bethesda, MD, USAPrincipal Investigator - Stephen W. Scherer - Hospital for Sick Children, Toronto, CanadaFunding Source - MH66766 - National Institutes of Health, Bethesda, MD, USAPrincipal Investigator - Bernie Devlin - University of Pittsburgh School of Medicine, Pittsburgh, PA, USAFunding Source - HD35465 - National Institutes of Health, Bethesda, MD, USAFunding Source - MH066673 - National Institutes of Health, Bethesda, MD, USAFunding Source - HD055784 - National Institutes of Health, Bethesda, MD, USAFunding Source - NS026630 - National Institutes of Health, Bethesda, MD, USAFunding Source - MH55284 - National Institutes of Health, Bethesda, MD, USAFunding Source - MH06359 - National Institutes of Health, Bethesda, MD, USAFunding Source - NS049261 - National Institutes of Health, Bethesda, MD, USAFunding Source - MH57881 - National Institutes of Health, Bethesda, MD, USAFunding Source - MH52708 - National Institutes of Health, Bethesda, MD, USAFunding Source - Grant: Po 255/17-4 - Deutsche Forschungsgemeinschaft, GermanyFunding Source - TMF/DA/5801 - Royal Netherlands Academy of Arts and SciencesFunding Source - MH081754 - National Institutes of Health, Bethesda, MD, USAdbGaPALCOHOL DEHYDROGENASE, big, TAPETUM 1, Autistic Spectrum, Feature, Mbp1, supernumerary, Charts., dIKK-gamma, froggy, prevention, Gyltl1a, Relative, Gus, large, Gur, Gut, TAPETUM1, Associations, DmIKK-gamma, dmIKKgamma, IKK[[gamma]], myd, prevention and control, IKKg, KEY, Key, increased, reference sample, MDDGB6, ASD, Mbp-1, LARGE, Autistic Spectrum Disorder, Atrial septal defect, genetic, preventive measures, BPFD#36, TA1, Autism Spectrum Disorders, g, IKK, Disorder, great, heterogeneity, asd, genomic copy number variation, Characteristics, Nucleotide, constitutitional genetic, Controlled, Controlling, data, preventive therapy, gyltl1b-b, Autistic behaviours, familial, copy number variation, 3.1.6.-, IKKgamma, DmIKKgamma, Characteristic, dIKK, MDDGA6, mKIAA0609, Relative Risks, Kenny, Autism spectrum disorders, rare (European definition), KIAA0609, nucleotides, Relative Risk, fg, susceptibility, AI747421, gyltl1b, Risk, Dmikkgamma, Autistic behaviors, prophylaxis, increased number, Risks, mdc1d, IKK-gamma, Gus-u, expanded, Gus-t, Gus-s, Gus-r, CG16910, Features, Autistic Spectrum Disorders, present in greater numbers in organism, MDC1D, metastatic, DmelCG16910, enr, enlarged, atypical autism, control, Autism spectrum disorder, interatrial communication, inherited genetic, hereditary, accessoryfalseAutism Genome Project (AGP) Consortium - GWAS - Stage I and II<p>Autism spectrum disorders (ASDs) are highly heritable (~90%), yet the underlying genetic determinants are largely unknown. To understand the genetic and phenotypic heterogeneity in ASDs, we analyzed 2,611 strictly defined ASD families with over 1,000,000 single nucleotide polymorphisms (SNPs), and applied multiple analytical strategies to examine these families for SNPs and Copy Number Variation (CNVs) affecting risk for ASDs. Secondary analyses examined associations in more homogenous subgroups. Furthermore, the use of large control datasets permitted contrasting case and control samples and addressed the potential increased burden of rare CNVs in ASD. Our data have allowed us to discern key features of the ASD genomic architecture, find new susceptibility loci, and chart a course for future studies in ASDs.</p>2016-03-022016-03-02phs000267Autism Spectrum Disorders2284350420663923186320901732288020531469