Discovery of early life causes of autism spectrum disorder through retrospective metabolomics and proteome analysis of teeth
通过牙齿的回顾性代谢组学和蛋白质组分析发现自闭症谱系障碍的早期原因
基本信息
- 批准号:10000917
- 负责人:
- 金额:$ 25.43万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2019
- 资助国家:美国
- 起止时间:2019-09-01 至 2022-07-31
- 项目状态:已结题
- 来源:
- 关键词:1 year oldAddressAffectBiochemicalBiologicalBiological AssayBiological MarkersBloodChemicalsChildChild HealthChildhood Acute Lymphocytic LeukemiaClinicalDataDevelopmentDevelopmental BiologyDiagnosisDiseaseEarly DiagnosisEmerging TechnologiesEnvironmental ExposureEnvironmental Risk FactorEtiologyEventExposure toEye MovementsFoundationsGeneticGoalsGrowthIncidenceIndividualInflammationInvestigationKnowledgeLaboratoriesLifeLinkMapsMeasurementMeasuresMetabolicMetabolismMetalsMethodologyMethodsNeonatalNeurobiologyNeurologic ProcessNutrientOnset of illnessOxidative StressParticipantPathway interactionsPopulationPredispositionPregnancyPrevalenceProcessProtein AnalysisProteinsProteomeProteomicsPublic HealthQuestionnairesSample SizeSamplingSecond Pregnancy TrimesterSiblingsStatistical MethodsStressSumTechniquesTechnologyTestingThird Pregnancy TrimesterTimeTooth DiseasesTooth structureToxic effectTreesTwin Multiple BirthUmbilical Cord BloodWorkautism spectrum disorderbasebrain morphologycase controlcohortdesigndisorder riskearly childhoodearly life exposureenvironmental chemicalfetalhigh dimensionalityinsightinterestmetabolomemetabolomicsmetal metabolismnovelpostnatal developmentpostnatal periodprenatalprenatal exposureresponsesmall moleculetemporal measurementtherapeutic targettreatment strategy
项目摘要
Summary/Abstract:
Autism spectrum disorder (ASD) is a heterogeneous disease with an unknown etiology. The global increase in
ASD incidence suggests that genetics alone is unlikely to be the major driver of ASD, but that the increased
prevalence is likely due to altered exposures to environmental factors. In fact, we know that numerous
environmental exposures (nutrients, chemicals, stress, etc.) impact child health, typically exerting their toxicity
through either metabolites or perturbations in endogenous pathways, making metabolomics and protein
analysis key emerging technologies to elucidate the relationships between these exposures and ASD. But how
do we directly measure these early life exposures? Central to our study is the use of novel tooth matrix
biomarkers, which take advantage of the incremental manner (similar to tree growth rings) of the
developmental biology of teeth. The techniques that we have developed allow us to temporally distinguish
exposure between the 2nd trimester, 3rd trimesters, and postnatal periods, enabling identification of the
sensitive life stages for biological perturbations in fetal and neonatal development most strongly associated
with ASD risk. For the present application, we will perform the first untargeted metabolomics analysis of ASD
teeth to delineate unique alterations in corresponding autism and non-autism children. This will be supported
by the first targeted highly multiplexed protein analysis of teeth (92 proteins) for delineating biological pathways
of interest, including inflammation, oxidative stress and those associated with neurobiological processes. We
will use novel statistical methodology, weighted quantile sum regression (WQS) that addresses time-varying
effects of high-dimensional mixtures, and increases power when compared to traditional methods to discover
biomarkers and biological pathways associated with ASD. Discovery will be performed on 40 ASD case-control
sibling pairs, and replication on an independent population of 35 unrelated case-control pairs. Our method is a
non-invasive advancement in technology to obtain direct and repeated measures of biomarkers associated
with early life etiology of ASD.
摘要/文摘:
项目成果
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{{ truncateString('Syam S Andra', 18)}}的其他基金
Discovery of early life causes of autism spectrum disorder through retrospective metabolomics and proteome analysis of teeth
通过牙齿的回顾性代谢组学和蛋白质组分析发现自闭症谱系障碍的早期原因
- 批准号:
9809324 - 财政年份:2019
- 资助金额:
$ 25.43万 - 项目类别:
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