Dataset Information

Identification of genetic loci underlying the phenotypic constructs of autism spectrum disorders.

ABSTRACT: To investigate the underlying phenotypic constructs in autism spectrum disorders (ASD) and to identify genetic loci that are linked to these empirically derived factors.Exploratory factor analysis was applied to two datasets with 28 selected Autism Diagnostic Interview-Revised (ADI-R) algorithm items. The first dataset was from the Autism Genome Project (AGP) phase I (1,236 ASD subjects from 618 families); the second was from the AGP phase II (804 unrelated ASD subjects). Variables derived from the factor analysis were then used as quantitative traits in genome-wide variance components linkage analyses.Six factors, namely, joint attention, social interaction and communication, nonverbal communication, repetitive sensory-motor behavior, peer interaction, and compulsion/restricted interests, were retained for both datasets. There was good agreement between the factor loading patterns from the two datasets. All factors showed familial aggregation. Suggestive evidence for linkage was obtained for the joint attention factor on 11q23. Genome-wide significant evidence for linkage was obtained for the repetitive sensory-motor behavior factor on 19q13.3.This study demonstrates that the underlying phenotypic constructs based on the ADI-R algorithm items are replicable in independent datasets, and that the empirically derived factors are suitable and informative in genetic studies of ASD.

SUBMITTER: Liu XQ

PROVIDER: S-EPMC3593812 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Identification of genetic loci underlying the phenotypic constructs of autism spectrum disorders.

Liu Xiao-Qing XQ Georgiades Stelios S Duku Eric E Thompson Ann A Devlin Bernie B Cook Edwin H EH Wijsman Ellen M EM Paterson Andrew D AD Szatmari Peter P

Journal of the American Academy of Child and Adolescent Psychiatry 20110701 7

<h4>Objective</h4>To investigate the underlying phenotypic constructs in autism spectrum disorders (ASD) and to identify genetic loci that are linked to these empirically derived factors.<h4>Method</h4>Exploratory factor analysis was applied to two datasets with 28 selected Autism Diagnostic Interview-Revised (ADI-R) algorithm items. The first dataset was from the Autism Genome Project (AGP) phase I (1,236 ASD subjects from 618 families); the second was from the AGP phase II (804 unrelated ASD s ...[more]

PMID: 21703496

Similar Datasets

Project description:Autism spectrum disorders (ASD) are neurodevelopmental disorders characterized by delayed/abnormal language development, deficits in social interaction, repetitive behaviors and restricted interests. The heterogeneity in clinical presentation of ASD, likely due to different etiologies, complicates genetic/biological analyses of these disorders. DNA microarray analyses were conducted on 116 lymphoblastoid cell lines (LCL) from individuals with idiopathic autism who are divided into 3 phenotypic subgroups according to severity scores from the commonly used Autism Diagnostic Interview-Revised questionnaire and age-matched, nonautistic controls. Statistical analyses of gene expression data from control LCL against that of LCL from ASD probands identify genes for which expression levels are either quantitatively or qualitatively associated with phenotypic severity. Comparison of the significant differentially expressed genes from each subgroup relative to the control group reveals differentially expressed genes unique to each subgroup as well as genes in common across subgroups. Among the findings unique to the most severely affected ASD group are genes that regulate circadian rhythm, which has been shown to have multiple effects on neurological as well as metabolic functions commonly dysregulated in autism. Among the genes common to all 3 subgroups of ASD are 5 novel genes which appear to associate with androgen sensitivity, which may underlie the strong 4:1 bias towards affected males. Gene expression profiling of 116 LCL from autistic (87) and nonautistic (29) individuals were obtained using a custom-printed DNA microarray containing 39,936 elements (TIGR 40K Human array, GPL3427) and a reference design in which each sample was compared to the Stratagene Universal Human RNA standard. The 87 autistic samples were divided into phenotypic subgroups (language, mild, savant) on the basis of cluster analyses of scores from an autism diagnostic questionnaire, the Autism Diagnostic Interview-Revised instrument. Differentially expressed genes were determined for all autistic vs. control groups, as well as for each of 3 phenotypic ASD groups and controls.

Dataset Information

Identification of genetic loci underlying the phenotypic constructs of autism spectrum disorders.

Publications

Identification of genetic loci underlying the phenotypic constructs of autism spectrum disorders.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure