3/3 Genetic Analysis of the International Cohort Collection for Bipolar Disorder

双相情感障碍国际队列收集的 3/3 遗传分析

基本信息

批准号：
8863507
负责人：
JORDAN W SMOLLER
金额：
$ 17.4万
依托单位：
MASSACHUSETTS GENERAL HOSPITAL
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-04-15 至 2018-01-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8863507
关键词：
Affect Affective African American Age of Onset Alleles Architecture Biology Bipolar Disorder Boston California Cataloging Catalogs ChIP-seq Characteristics Chronic Clinical Clinical Data Code Collaborations Collection Complex Copy Number Polymorphism DNA Library DRD2 gene Data Data Analyses Detection Differential Diagnosis Dimensions Disease Dopamine Receptor Etiology European Funding General Hospitals Generations Genes Genetic Genetic Fingerprintings Genetic Heterogeneity Genetic Polymorphism Genomics Genotype Goals Grant Human Individual Institutes International Investments Joints Knowledge Latino Learning Major Depressive Disorder Maps Massachusetts Measures Memory Mental disorders Meta-Analysis Methods Modeling Moods National Institute of Mental Health Neurocognition Neurocognitive Neuropharmacology Nucleotides Panic Disorder Pathway interactions Personality Phenotype Philanthropic Fund Psychotic Disorders Quality Control Research Research Personnel Risk Risk Factors Sample Size Sampling Sampling Studies Schizophrenia Single Nucleotide Polymorphism Site Statistical Methods Subgroup Substance Use Disorder Suicide Time Universities Variant Work affective psychoses base case control cognitive ability cohort cost effective disorder risk disorder subtype exome exome sequencing genetic analysis genetic association genome wide association study genome-wide genotyping technology indexing innovation insight novel predictive modeling processing speed rare variant response risk variant sample collection

项目摘要

DESCRIPTION (provided by applicant): The grant, "Genetic Analysis of the International Cohort Collection for Bipolar Disorder", is continuation of a long-standing collaborative effort funded in response to an RFA for sample collections in bipolar disorder. We are thus submitting the current new application from the original group of investigators to continue the collaboration and proceed to its next logical step analyses of data being generated. We developed the "International Cohort Collection for Bipolar Disorder" in response to a NIMH FOA MH08-130. Under the auspices of R01MH085542 (Smoller/Sklar, PIs) and philanthropic funding we implemented a phenotypically robust, rapid, and cost effective method for sample collection. During the five years of the grant we have banked DNA from ~18,000 cases and 16,000 controls never previously used for genomic study of bipolar disorder (BD). We propose here enhanced aims in a unique sample to increase our knowledge of BD and to keep this highly productive team intact. The samples studied here will more than double the available samples for GWAS, and will be among the first to analyze rare variants using exome chip and exome sequencing. These analyses will provide substantially enhanced power for detection of networks and loci that confer BD risk. In Aim 1 we will perform a genomic characterization of an independent cohort of 15,800 cases and 18,598 controls to identify high confidence genetic loci for risk of BD through association study of common single nucleotide polymorphisms, copy number variants, and rare single nucleotide variants. We will further use the data to explore genetic prediction models for BD for two specific clinical scenarios. In Aim 2 we will apply these data to characterize the spectrum of genotype-phenotype relationships by examining phenotypic subgroups, cross- disorder relationships, quantitative personality dimensions, and neurocognition. Our goal is to learn more about the genetics of BD and how genes might act to alter disease risk. We propose to do this using the largest and most comprehensively studied sample collection in the field that includes both genetic and phenotypic risk factors.

描述（由申请人提供）：赠款是“国际躁郁症国际队列收集的遗传分析”，是为了响应RFA来响应于双相情感障碍的样本收集的长期合作努力。因此，我们正在从原始研究者小组中提交当前的新应用程序，以继续协作，并继续对正在生成的数据进行下一个逻辑步骤分析。我们开发了“国际躁郁症国际队列收集”，以响应NIMH FOA MH08-130。在R01MH085542（Smoller/Sklar，PIS）和慈善资金的主持下，我们实施了一种表型强大，快速且具有成本效益的样品收集方法。在赠款的五年中，我们已经从约18,000例病例和16,000个对照组中进行了DNA，以前从未用于基因组疾病研究（BD）。我们在这里提出了一个在独特的样本中增强目标，以提高我们对BD的了解，并保持这支高产的团队完整。这里研究的样品将是GWAS可用样品的两倍以上，并将是最早使用外显子芯片和外显子组测序分析稀有变体的人之一。这些分析将为检测网络和基因座的能力提供大幅增强的功能。在AIM 1中，我们将对15,800例病例和18,598个控制的独立队列进行基因组表征，我们将进一步使用数据探索两种特定临床场景的BD遗传预测模型。在AIM 2中，我们将通过检查表型亚组，跨序列关系，定量人格维度和神经认知来应用这些数据来表征基因型 - 表型关系的光谱。我们的目标是更多地了解BD的遗传学以及基因如何采取行动来改变疾病风险。我们建议使用包括遗传和表型危险因素的现场最大，最全面研究的样本收集来做到这一点。