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）：这项名为“双相情感障碍国际队列收集的基因分析”的资助是响应 RFA 资助的双相情感障碍样本收集的长期合作努力的延续，因此我们提交了原始小组当前的新申请。我们根据 NIMH FOA MH08-130 开发了“双相情感障碍国际队列收集”。在 R01MH085542（Smoller/Sklar，PI）和慈善资助的支持下，我们实施了一种表型稳健、快速且具有成本效益的样本收集方法。在资助的五年期间，我们存储了约 18,000 个病例和 16,000 个以前从未使用过的对照的 DNA。我们在此提出了一个独特样本的强化目标，以增加我们对双相情感障碍 (BD) 的了解并保持这一目标。这个高效的团队完好无损。这里研究的样本将是 GWAS 可用样本的两倍以上，并将成为首批使用外显子组芯片和外显子组测序分析罕见变异的样本之一。这些分析将为网络和基因座的检测提供显着增强的能力。在目标 1 中，我们将对 15,800 个病例和 18,598 个对照的独立队列进行基因组表征，通过常见单核苷酸的关联研究来识别 BD 风险的高置信度遗传位点。我们将使用这些数据进一步探索针对两种特定临床情况的 BD 遗传预测模型，通过检查来应用这些数据来表征基因型-表型关系的范围。我们的目标是更多地了解双相情感障碍的遗传学以及基因如何改变疾病风险。在该领域包括遗传和表型风险因素。