Dataset Information

The Broader Autism Phenotype in Mothers is Associated with Increased Discordance Between Maternal-Reported and Clinician-Observed Instruments that Measure Child Autism Spectrum Disorder.

ABSTRACT: Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician-observed instruments. Sometimes, results between these instruments disagree. The broader autism phenotype (BAP) in parent-reporters may be associated with discordance. Study to Explore Early Development data (N?=?712) were used to address whether mothers with BAP and children with ASD or non-ASD developmental disabilities were more likely than mothers without BAP to 'over-' or 'under-report' child ASD on ASD screeners or interviews compared with clinician observation or overall impression. Maternal BAP was associated with a child meeting thresholds on a maternal-reported screener or maternal interview when clinician ASD instruments or impressions did not (risk ratios: 1.30 to 2.85). Evidence suggests acknowledging and accounting for reporting discordances may be important when diagnosing ASD.

SUBMITTER: Rubenstein E

PROVIDER: S-EPMC5728366 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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The Broader Autism Phenotype in Mothers is Associated with Increased Discordance Between Maternal-Reported and Clinician-Observed Instruments that Measure Child Autism Spectrum Disorder.

Rubenstein Eric E Edmondson Pretzel Rebecca R Windham Gayle C GC Schieve Laura A LA Wiggins Lisa D LD DiGuiseppi Carolyn C Olshan Andrew F AF Howard Annie G AG Pence Brian W BW Young Lisa L Daniels Julie J

Journal of autism and developmental disorders 20171001 10

Autism spectrum disorder (ASD) diagnosis relies on parent-reported and clinician-observed instruments. Sometimes, results between these instruments disagree. The broader autism phenotype (BAP) in parent-reporters may be associated with discordance. Study to Explore Early Development data (N = 712) were used to address whether mothers with BAP and children with ASD or non-ASD developmental disabilities were more likely than mothers without BAP to 'over-' or 'under-report' child ASD on ASD screene ...[more]

PMID: 28748335

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Project description:In families raising a child with an autism spectrum disorder (ASD), infant siblings are at elevated risk for ASD and other developmental concerns, including elements of the broader autism phenotype (BAP). Typically, the BAP is indexed using standardized developmental assessments; however, these measures do not capture a number of social difficulties commonly associated with the BAP. The present study aims to expand our developmental understanding of the BAP by comparing children exhibiting the BAP to their typically developing peers on, (a) standardized measures of development, and (b) social behaviors exhibited during dyadic play interactions. As part of a prospective study, dyads were recruited from families with at least one older child with ASD (high-risk, n = 36), and families with no history of ASD (low-risk, n = 38). During laboratory visits at 12, 15, 18, and 24 months of age, infants completed a series of standardized assessments and a mother-child play interaction. Dyadic play interactions were micro-analytically coded for gaze, positive affect, and vocalizations to create theory-driven composites to index dyadic synchrony and responsiveness. Videos were also coded with an existing rating scheme for joint engagement and child responsiveness. Multilevel models revealed significant group differences on select constructs within the first 2 years. Language and cognitive differences emerged by 24 months of age, whereas dyadic differences were evident as early as 15 months. Recognizing the increasing demand for elevated-risk interventions, these findings highlight several social constructs through which interventions may identify risk and promote optimal development. Autism Res 2019, 12: 469-481 © 2019 International Society for Autism Research, Wiley Periodicals, Inc. LAY SUMMARY: In families raising children with an autism spectrum disorder (ASD), younger siblings are at an increased risk for social and developmental difficulties that characterize a "broader autism phenotype." The present study explored the emergence of social, language, and cognitive differences in the first 2 years of life. Social differences were evident as early as 15 months of age for several play-based measures, and language and cognitive differences emerged by 24 months of age. For infant siblings of children with ASD, some of the earliest behavioral marks for subclinical features of ASD are evident within the first 2 years of life.

Project description:BackgroundEstablishment and maintenance of DNA methylation throughout the genome is an important epigenetic mechanism that regulates gene expression whose disruption has been implicated in human diseases like cancer. It is therefore crucial to know which genes, or other genomic features of interest, exhibit significant discordance in DNA methylation between two phenotypes. We have previously proposed an approach for ranking genes based on methylation discordance within their promoter regions, determined by centering a window of fixed size at their transcription start sites. However, we cannot use this method to identify statistically significant genomic features and handle features of variable length and with missing data.ResultsWe present a new approach for computing the statistical significance of methylation discordance within genomic features of interest in single and multiple test/reference studies. We base the proposed method on a well-articulated hypothesis testing problem that produces p- and q-values for each genomic feature, which we then use to identify and rank features based on the statistical significance of their epigenetic dysregulation. We employ the information-theoretic concept of mutual information to derive a novel test statistic, which we can evaluate by computing Jensen-Shannon distances between the probability distributions of methylation in a test and a reference sample. We design the proposed methodology to simultaneously handle biological, statistical, and technical variability in the data, as well as variable feature lengths and missing data, thus enabling its wide-spread use on any list of genomic features. This is accomplished by estimating, from reference data, the null distribution of the test statistic as a function of feature length using generalized additive regression models. Differential assessment, using normal/cancer data from healthy fetal tissue and pediatric high-grade glioma patients, illustrates the potential of our approach to greatly facilitate the exploratory phases of clinically and biologically relevant methylation studies.ConclusionsThe proposed approach provides the first computational tool for statistically testing and ranking genomic features of interest based on observed DNA methylation discordance in comparative studies that accounts, in a rigorous manner, for biological, statistical, and technical variability in methylation data, as well as for variability in feature length and for missing data.

Dataset Information

The Broader Autism Phenotype in Mothers is Associated with Increased Discordance Between Maternal-Reported and Clinician-Observed Instruments that Measure Child Autism Spectrum Disorder.

Publications

The Broader Autism Phenotype in Mothers is Associated with Increased Discordance Between Maternal-Reported and Clinician-Observed Instruments that Measure Child Autism Spectrum Disorder.

Similar Datasets

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