权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Placental Transcriptomics and Risk for Schizophrenia

胎盘转录组学和精神分裂症的风险

基本信息

批准号：
10321945
负责人：
Gianluca Ursini
金额：
$ 18.1万
依托单位：
LIEBER INSTITUTE, INC.
依托单位国家：
美国
项目类别：
财政年份：
2020
资助国家：
美国
起止时间：
2020-12-24 至 2023-11-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10321945
关键词：
Accounting Affect Animals Area Behavior Biological Markers Biological Process Birth Blood Brain Diseases Child Data Detection Development Discipline of obstetrics Disease Epidemiology Exposure to Female Gene Expression Genes Genetic Genetic Markers Genetic Risk Genetic Variation Genome Genomics Genotype Goals Human Hydrocortisone Immune response Individual Infant Inflammation Lead Life Link Measures Mediating Mediator of activation protein Methodology Molecular Morbidity - disease rate Nature Neonatal Newborn Infant Outcome Pathway Analysis Pathway interactions Perinatal Physiology Placenta Placental Biology Placentation Pre-Clinical Model Predisposition Pregnancy Pregnancy Complications Pregnancy Outcome Premature Birth Prevention Prevention strategy Process Protein Isoforms Proteins Questionnaires RNA Splicing Relative Risks Research Risk Risk Factors Role Salivary Sampling Schizophrenia Stress Testing Transcript Translating Weight Work base case control cell type cohort disorder risk epidemiology study fetal genetic risk factor genomic predictors high risk innovation insight male maternal stress neurobehavior neurodevelopment neurodevelopmental effect novel novel strategies offspring perinatal complications polygenic risk score postnatal precision medicine prenatal preservation prevent risk variant schizophrenia risk sex tool transcriptome transcriptome sequencing transcriptomics

项目摘要

Our main objective is to find the factors mediating the relationship between genetic risk factors, complications in early life (ELCs, i.e. pre-, and perinatal) and altered neuro- development (ND) in humans, so that, in high-risk individuals, disorders of ND such as schizophrenia (SZ), can be prevented or rescued in early stages. Epidemiological findings show that ELCs increase the risk for ND disorders including SZ; preclinical models show that ELCs alter ND, an effect partially mediated by gene expression in placenta, with males more vulnerable than females. However, the mechanism linking ELCs with SZ are still elusive. Our recent human work found that genetic factors converge with placenta biology in affecting risk for SZ. Here, we focus on detecting the molecular mediators involved: that is, the molecules that, by regulating placenta's physiology, regulate ND, drive susceptibility to SZ, and may mediate the interaction between genetic factors and ELCs on the risk for the disorder. We propose a multi-step strategy, which leverages our strengths in analyzing transcriptomic and genetic data, using well-established and innovative methodologies to explore a novel area of research: the relationship between genomic risk factors, placenta and SZ. We will first investigate the transcriptomic correlates of genetic risk factors for SZ in the placenta, and we will analyze whether gene isoforms associated with risk for SZ are co-expressed in placenta, as part of specific biological processes. Using genotype-based prediction of gene expression in large cohorts, we will identify the specific placental isoforms associated with SZ case-control status. We will then generate placental genomic predictors of SZ risk, and we will test their relationship with ND outcomes. To investigate sex-specific placental processes relevant for SZ, we will stratify each analysis by sex. We expect our data to converge in identifying placental molecules and pathways that are relevant for SZ. The detection of such molecules may be translated into the development of novel prenatal prevention of SZ, aimed at preserving / optimizing the important placental support to ND, and the development of novel postnatal prevention, based on the identification of high-risk individuals – through placental and genetic biomarkers.

我们的主要目标是找到介导遗传风险之间关系的因素