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The Bipolar Sequencing Consortium for Combined Analyses and Follow-Up

用于组合分析和随访的双极测序联盟

基本信息

批准号：
9156179
负责人：
MICHAEL L BOEHNKE
金额：
$ 89.54万
依托单位：
JOHNS HOPKINS UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2016
资助国家：
美国
起止时间：
2016-08-01 至 2019-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/9156179
关键词：
Affect Architecture Biological Bipolar Disorder Case-Control Studies Collaborations Collection Communities Complex Country Data Data Analyses Data Set Disease Ensure Etiology Extended Family Family Family Study Foundations Gene Frequency Genes Genetic Genetic Predisposition to Disease Genetic Risk Genetic Variation Genomics Goals Heritability Individual Investments Joints Mental disorders Minor Molecular Mood Disorders National Institute of Mental Health Play Prevention strategy Proteomics Public Health Reporting Research Research Design Research Infrastructure Research Personnel Resource Sharing Resources Risk Role Sampling Schizophrenia Susceptibility Gene Technology Testing Variant Work case control data sharing disorder control disorder risk exome sequencing follow-up genetic association genetic variant genome sequencing genome wide association study improved meetings neurobiological mechanism next generation sequencing rare variant research study severe mental illness success transcriptomics whole genome working group

项目摘要

This proposal seeks crucial support for The Bipolar Sequencing Consortium (BSC), which brings together leading researchers from around the country and internationally who are carrying out exome and genome sequencing studies of bipolar disorder (BD). BD is a devastating mood disorder that imposes a significant burden on public health. It is among the most heritable serious mental disorders, with estimates ranging up to 90%. Yet, success in identifying susceptibility genes for BD has lagged noticeably behind other serious mental disorders such as schizophrenia. In this proposal, the BSC will share resources and sequence data for combined analyses that will advance the search for the genetic etiology of BD at a scale not possible by each of the research groups working by themselves. Recent efforts by the Psychiatric Genomics Consortium (PGC) using genome-wide association studies (GWAS) have begun to implicate common genetic variation in the risk for BD. However, GWAS miss the contribution of rarer genetic variation with minor allele frequencies <1%. It is hypothesized that rarer genetic variation may further contribute to the heritability of complex disorders like BD, and that identification of rarer genetic variation may more directly implicate underlying biological mechanisms in the etiology of BD. Advances in next generation sequencing technology are making it increasingly possible to sequence the exome or entire genome in large numbers of individuals in a costeffective manner. With this technology, studies can now interrogate the full spectrum of genetic variation and correlate it with disease. Researchers in the BSC are taking advantage of next generation sequencing to study BD in families with multiple affected relatives or in large numbers of unrelated cases and controls. In this proposal, we will assemble the largest existing collection of sequencing data on BD and carry out combined analyses of over 4,700 cases and 9,000 controls from 5 different case-control sequencing studies and over 200 families with over 1,000 affected relatives from 10 family sequencing studies. We will integrate the findings from the combined analyses with other on-going genomic, transcriptomic and proteomic studies to clarify the role of rare variants in the genetic architecture of BD and characterize the molecular and neurobiological mechanisms by which implicated rare variants and genes may contribute to risk for BD. We will then follow-up the top findings from our analyses and test them in an independent sample of over 5,000 cases and controls that will be made available to us through a new whole genome sequencing initiative. All summary data and results from the combined analyses will be freely shared via an on-line study resource with the research community. Next generation sequencing technology holds great promise for revealing the genetic architecture of complex psychiatric disorders. This proposal will build on the NIMH's considerable investment in sequencing to maximize our ability to explain the genetic contribution to BD and lay the needed foundation for improved treatment/prevention strategies.

该提案寻求双相测序联盟（BSC）的关键支持，该联盟汇集了