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A Family-Genetic Study of Language in Autism

自闭症语言的家族遗传学研究

基本信息

批准号：
10739167
负责人：
Molly C Losh
金额：
$ 71.14万
依托单位：
NORTHWESTERN UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2023
资助国家：
美国
起止时间：
2023-09-01 至 2028-06-30
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10739167
关键词：
Address Auditory Behavioral Biological Biological Markers Biology Clinical Clinical Investigator Clinical Research Clinical Trials Cognitive Complex Control Groups Data Development Diagnostic Dimensions Electrophysiology (science)Employment Etiology FMR1 Family Family Study Female First Degree Relative Friendships Funding Future Genetic Genetic Diseases Genetic Markers Genetic Variation Genetic study Grain Heritability Heterogeneity Impairment Individual Informatics Intervention Language Language Disorders Life Link Longevity Machine Learning Measurement Measures Methods Modality Molecular Genetics Mutation Parents Participant Pattern Phenotype Process Psycholinguistics Research Research Design Research Personnel Resources Rest Risk Sampling Sex Differences Site Social Environment Speech Speech Sound Subgroup Symptoms Translating Variant Visual Work analytical method analytical tool autism community autism spectrum disorder behavioral phenotyping biobank biological research clinical application clinical practice clinically significant cohort data harmonization data repository data sharing differential expression family genetics gaze genetic analysis girls improved individuals with autism spectrum disorder innovation language impairment male molecular marker multidisciplinary multimodality neglect neural neural correlate neurophysiology pragmatic study predict clinical outcome prevent risk variant segregation skills social social skills sound speech processing symptomatology theories tool trait translational goal

项目摘要

Project Summary Pragmatic (i.e., social) language deficits are a defining feature of autism spectrum disorder (ASD), which can impose significant burden on individuals throughout the lifespan. Strong evidence also suggests that this clinical domain is influenced by genetic liability to ASD in unaffected relatives, constituting a principal component of the broad autism phenotype (BAP) and linked with increased polygenic risk for ASD in unaffected relatives. Pragmatic language features of ASD also show significant overlap with phenotypes observed in carriers of FMR1 mutations, implicating this highly penetrant ASD risk gene in the pragmatic language phenotype of ASD in particular. The pragmatic language domain is therefore not only highly clinically significant in ASD, but also sensitive to underlying ASD genetic liability, making this skill an important target for understanding the biological origins of ASD and its component features, with potentially important clinical applications. In this competing renewal, we will apply innovative deep phenotyping methods and an armamentarium of complementary analytic platforms to dissect the contributors to pragmatic language impairments in ASD and their biological basis. Using a family-study design and including a representative ASD cohort enriched for girls, ASD parents, and respective control groups, we will characterize ASD-related pragmatic profiles that extend beyond traditional, categorically- defined diagnostic boundaries, which may be linked with distinct neural signatures and molecular genetic variation. Aim 1 will apply both hypothesis- and data-driven analytic approaches to analyze a comprehensive battery assessing component skills contributing to pragmatic impairments in ASD, and subclinical pragmatic differences in the BAP among parents. Aim 2 will employ a battery of targeted electrophysiological measures to examine potential neural correlates of pragmatic impairment in ASD and the BAP. Finally, Aim 3 will evaluate the relationship between behavioral and neural phenotypic signatures obtained in Aims 1 and 2, respectively, and FMR1-related genetic variation. Our preliminary studies demonstrated a complex network of skills contributing to pragmatic impairments in ASD that may be sensitively measured with the advanced fine-grained computational- and machine-learning-based approaches proposed in this project, with compelling ties to neurophysiological and molecular genetic correlates that will be measured in this project. Together, the rich and extensive data produced will contribute to the understanding of the fine-grained skills that contribute to the heterogeneity in ASD, and the mechanistic and biological origins of this important clinical domain. Our findings will move us closer to achieving our long-term translational goal: to advance our understanding of the causes of the pragmatic language impairment in ASD in order to improve prediction of clinical outcomes and help guide future interventions and treatment in ASD.

项目总结

项目成果

期刊论文数量（16）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Quantifying narrative ability in autism spectrum disorder: a computational linguistic analysis of narrative coherence.

DOI：
10.1007/s10803-014-2158-y
发表时间：
2014-12
期刊：
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
影响因子：
3.9
作者：
Losh, Molly;Gordon, Peter C.
通讯作者：
Gordon, Peter C.

Neural Processing of Speech Sounds in ASD and First-Degree Relatives.

DOI：
10.1007/s10803-022-05562-7
发表时间：
2023-08
期刊：
JOURNAL OF AUTISM AND DEVELOPMENTAL DISORDERS
影响因子：
3.9
作者：
Patel, Shivani P.;Winston, Molly;Guilfoyle, Janna;Nicol, Trent;Martin, Gary E.;Nayar, Kritika;Kraus, Nina;Losh, Molly
通讯作者：
Losh, Molly

A constellation of eye-tracking measures reveals social attention differences in ASD and the broad autism phenotype.