Neurodevelopment: Genes, Environment, and their Interactions

神经发育：基因、环境及其相互作用

• 批准号: 9271089
• 负责人: Laura A. Almasy
• 金额: $ 40.78万
• 依托单位: UNIVERSITY OF TEXAS RIO GRANDE VALLEY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-08-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9271089
• 关键词: Adolescent; Age; Aging; Behavior; Behavioral Genetics; Biological; Biological Process; Biomedical Research; Bipolar Disorder; Brain; Child; Childhood; Chromosome Mapping; Clinical; Cognition; Cognitive; Complex; Data Set; Development; Developmental Process; Diffusion Magnetic Resonance Imaging; Disease; Environment; Environmental Risk Factor; Event; Exhibits; Functional Magnetic Resonance Imaging; Functional disorder; Genes; Genetic; Genome; Genotype; Goals; Gur; Heritability; Human; Individual; Interview; Lead; Life; Major Depressive Disorder; Measures; Mediating; Medical History; Mental disorders; Modeling; Neuroanatomy; Neurocognition; Neurocognitive; Neuropsychology; Participant; Pennsylvania; Performance; Phenotype; Philadelphia; Physiology; Process; Psychiatry; Psychopathology; Research Institute; Risk; Role; Sampling; Schizophrenia; Schools; Source; Testing; Texas; Universities; Variant; Youth; age related; associated symptom; brain behavior; cognitive ability; cohort; computerized; demographics; design; emerging adult; gene environment interaction; genetic analysis; genome wide association study; genome-wide; indexing; multimodality; neurobehavioral; neurodevelopment; neuroimaging; neurophysiology; neuropsychiatry; novel; pleiotropism; public health relevance; screening; stressor; symptomatology; trait

 DESCRIPTION (provided by applicant): The goal of this study is to localize and characterize genes that influence normal maturation-related changes in neurocognitive, neuroanatomic and neurophysiological indices. A substantial number of brain-related traits exhibit gene by age interactions, suggesting a heritable basis for neurocognitive, neuroanatomic and neurophysiological changes with age and highlighting the potential role of genes in differential brain maturation. We will utilize novel analytical approaches to investigate genetic and environmental influences on variation in brain, cognition, and behavior from a developmental perspective, modeling complex effects in both the genetic and environmental realms, and potential interactions between them, while allowing for changes in these effects across development, in the Philadelphia Neurodevelopmental Cohort (PNC). The PNC includes ~9500 individuals between the ages of 8 - 21 years who have been characterized for brain, behavior, and genetic variables. All participants were assessed neuropsychiatrically and completed a Computerized Neurocognitive Battery (CNB). Interviews included assessment of demographics, life events and stressors, school performance, medical history, and screening for psychopathology and presence and duration of associated symptoms. The CNB included an estimate of IQ as well as 14 tests designed to assess five neurobehavioral functions. A subset of ~1450 participants underwent neuroimaging, including structural and functional MRI and diffusion tensor imaging. Approximately 8700 PNC participants have been genotyped for 500K - 950K genome-wide SNPs, obtained on a diverse variety of genotyping platforms. The large size of this data set, combined with the rich and detailed assessments in a variety of phenotypic domains, provides an unparalleled opportunity to study gene-by-age and gene-by-environment interactions in neurodevelopment and their potential contribution to risk of mental illness. The specific aims of the proposed study are to: 1) Localize genes influencing variation in neurodevelopment in the PNC; 2) Assess whether these genetic effects change with age and identify additional loci exhibiting gene- by-age interactions; and 3) Assess complex environmental effects on neurodevelopment and test whether they interact with, and moderate or mediate, genetic effects. Laura Almasy, Texas Biomedical Research Institute, is contact PI of this application and co-PIs David Glahn, Yale University, and Raquel Gur, University of Pennsylvania, will lead subcontracts. Dr. Almasy provides expertise in genetic analysis of complex phenotypes, including gene-by-age and gene-by-environment interactions. Drs. Glahn and Gur provide expertise in cognitive neuropsychology, neuroimaging, and psychiatry.

 描述（由申请人提供）：本研究的目的是定位和表征影响神经认知、神经解剖学和神经生理学指标的正常成熟相关变化的基因。大量的脑相关性状表现出基因与年龄的相互作用，这表明神经认知，神经解剖学和神经生理学的变化与年龄的遗传基础，并突出了基因在不同的大脑成熟的潜在作用。我们将利用新的分析方法，从发展的角度研究遗传和环境对大脑，认知和行为变化的影响，在遗传和环境领域建模复杂的影响，以及它们之间的潜在相互作用，同时允许在费城神经发育队列（PNC）中，这些影响在整个发展过程中发生变化。PNC包括约9500名年龄在8 - 21岁之间的个体，他们的大脑，行为和遗传变量已经被表征。所有参与者都接受了神经精神病学评估并完成了计算机神经认知测试（CNB）。访谈包括人口统计学、生活事件和压力源、学校表现、病史和精神病理学筛查以及相关症状的存在和持续时间的评估。CNB包括对智商的估计以及旨在评估五种神经行为功能的14项测试。约1450名受试者接受了神经成像，包括结构和功能MRI以及扩散张量成像。大约8700名PNC参与者已经进行了500 K-950 K全基因组SNP的基因分型，这些SNP是在各种基因分型平台上获得的。该数据集的庞大规模，加上在各种表型领域的丰富和详细的评估，为研究神经发育中基因与年龄和基因与环境的相互作用及其对精神疾病风险的潜在贡献提供了无与伦比的机会。拟议研究的具体目的是：1）定位影响PNC中神经发育变异的基因; 2）评估这些遗传效应是否随年龄变化，并确定表现出基因与年龄相互作用的其他基因座; 3）评估复杂的环境对神经发育的影响，并测试它们是否与遗传效应相互作用，以及是否调节或介导遗传效应。德克萨斯生物医学研究所的Laura Almasy是本申请的联系PI，耶鲁大学的共同PI大卫Glahn和宾夕法尼亚大学的Raquel Gur将领导分包合同。Almasy博士在复杂表型的遗传分析方面提供专业知识，包括基因与年龄和基因与环境的相互作用。Glahn和Gur博士提供认知神经心理学，神经影像学和精神病学方面的专业知识。