3/5-The Psychiatric GWAS Consortium: Integrated & Coordinated GWAS Meta-Analyses

3/5-精神病学 GWAS 联盟：综合

• 批准号: 7690003
• 负责人: Mark Joseph Daly
• 金额: $ 12.01万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-30 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7690003
• 关键词: Abbreviations; Administrator; Alcohols; American; Anorexia Nervosa; Appendix; Architecture; Area; Attention; Attention deficit hyperactivity disorder; Autistic Disorder; Bioinformatics; Biological; Bipolar Disorder; Body Height; Brain; Budgets; Caring; Charge; Classification; Clinical; Collaborations; Committee Members; Communication; Communities; Complex; Computer Analysis; Computers; Conflict (Psychology); Confusion; Consensus; Country; DSM-IV; Data; Data Set; Databases; Dependence; Deposition; Diagnosis; Diagnostic; Diagnostic and Statistical Manual; Disease; Electronic Mail; Ensure; Equilibrium; Etiology; European; Family; Foundations; Funding; Genetic; Genomics; Genotype; Glues; Heterogeneity; High Performance Computing; Human Genetics; Illicit Drugs; Individual; Institution; International; International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10); Internet; Joints; Jordan; Journals; Knowledge; Leadership; Left; Linux; Major Depressive Disorder; Manuscripts; Mental disorders; Meta-Analysis; Metaphor; Modeling; National Institute of Mental Health; Nature; Netherlands; New York City; Nicotine; Non-Insulin-Dependent Diabetes Mellitus; Numbers; Outcome; Paralysed; Participant; Personal Satisfaction; Phenotype; Philosophy; Policies; Population; Procedures; Process; Protocols documentation; Psychiatry; Publications; Purpose; Quality Control; Recording of previous events; Recurrence; Request for Applications; Research; Research Personnel; Resources; Rights; Risk; Role; Running; SNP genotyping; Sampling; Schizophrenia; Science; Scientist; Secure; Source; Specific qualifier value; Staging; Stratification; System; Teleconferences; Telephone; Testing; Time; Title; Travel; Update; Variant; Voting; Week; Work; Writing; base; case control; cluster computing; concept; day; depressive symptoms; design; experience; genome wide association study; member; organizational structure; psychogenetics; repository; research study; response; trait

DESCRIPTION (provided by applicant): This application consists of five collaborative R01s submitted in response to NIMH RFA-MH-08-121, "Limited Competition for Data Deposition and Analyses of Genome Wide Association Studies of Mental Disorders (Collaborative R01)". These applications are from the Psychiatric GWAS Consortium (PGC). By the end of 2008, there will be GWAS data on 47 samples of individuals with either attention-deficit hyperactivity disorder (ADHD), autism (AUT), bipolar disorder (BIP), major depressive disorder (MDD), or schizophrenia (SCZ). Taken together, these GWAS constitute the largest biological experiment ever conducted in psychiatry - over 80,000 subjects (59,000 independent cases/controls and over 7700 family trios), ~500,000 SNP genotypes per subject, and ~40 billion total genotypes. Although the availability of GWAS data is highly attractive, there is a real risk of conflicting claims and confusion. GWAS meta-analysis for any disease is complex and requires considerable care and expertise in order to be done validly. Given the urgent need to know if there are replicable genotype-phenotype associations, a new type of collaboration is required. To accomplish these ends, we initiated the PGC in early 2007 to conduct rigorous and comprehensive within- and cross- disorder GWAS meta-analyses. The overall philosophy of the PGC is to be as inclusive, democratic, and rapid as possible. The PGC is well-underway with a coordinating committee, five disease working groups, a cross-disorder group, statistical analysis group, and a cluster computer for data warehousing and statistical analysis. 101 scientists from 11 countries and 48 institutions. It is remarkable that all but one eligible study is participating and that no one who has joined the PGC has left. The Specific Aims of the PGC are: (1) Within-disorder meta-analyses: conduct separate meta-analyses of all available GWAS data for ADHD, AUT, BIP, MDD, and SCZ to attempt to identify convincing genotype-phenotype associations. (2) Cross-disorder analyses: it is widely suspected that the clinically-derived DSM-IV and ICD-10 definitions may not have "carved nature at the joint" with respect to the fundamental genetic architecture. There are two sub-aims: (2a) Conduct meta-analysis to attempt to identify convincing genotype-phenotype associations that are common to =2 of ADHD, AUT, BIP, MDD, and SCZ. (2b) Convene an expert working group to convert epidemiological and genetic epidemiological evidence into rigorous and explicit hypotheses about overlap amongst these disorders. The analytic plan abides to current best practices for GWAS quality control and meta-analysis, particularly in its attention to investigating sources of heterogeneity. Statistical power should be superior to any prior study in psychiatric genetics. Results will be made available as soon as possible. Finally, the PGC proposes to abide as fully as possible with the NIH's GWAS data sharing policies and we provide a detailed data sharing plan and timetable.

描述（由申请人提供）：本申请由五个合作R 01组成，以响应NIMH RFA-MH-08-121“精神疾病全基因组关联研究的数据沉积和分析有限竞争（合作R 01）”。这些应用程序来自Psychiatric GWAS Consortium（PGC）。到2008年底，GWAS将收集到47个患有注意力缺陷多动障碍（ADHD）、自闭症（AUT）、双相情感障碍（BIP）、重度抑郁症（MDD）或精神分裂症（SCZ）的个体样本的数据。总的来说，这些GWAS构成了有史以来在精神病学中进行的最大的生物学实验-超过80，000名受试者（59，000名独立病例/对照和7700多个家庭三人组），每个受试者约500，000个SNP基因型，约400亿个总基因型。虽然GWAS数据的可用性非常有吸引力，但存在着相互冲突的声明和混淆的真实的风险。任何疾病的GWAS荟萃分析都是复杂的，需要相当多的护理和专业知识才能有效地完成。鉴于迫切需要知道是否存在可复制的基因型-表型关联，需要一种新型的合作。为了实现这些目标，我们在2007年初启动了PGC，进行严格和全面的内部和跨疾病GWAS荟萃分析。PGC的总体理念是尽可能包容、民主和快速。PGC正在进行中，有一个协调委员会，五个疾病工作组，一个交叉疾病组，统计分析组和一个用于数据仓库和统计分析的集群计算机。来自11个国家和48个机构的101名科学家。值得注意的是，除了一项合格的研究外，所有符合条件的研究都参加了，并且没有一个加入PGC的人离开。PGC的具体目的是：（1）疾病内荟萃分析：对ADHD、AUT、BIP、MDD和SCZ的所有可用GWAS数据进行单独的荟萃分析，以试图确定令人信服的基因型-表型关联。(2)交叉疾病分析：人们普遍怀疑，临床上衍生的DSM-IV和ICD-10定义在基本遗传结构方面可能没有“在关节处雕刻的性质”。有两个次级目标：（2a）进行荟萃分析，试图确定ADHD、AUT、BIP、MDD和SCZ中≥ 2种常见的令人信服的基因型-表型关联。(2b)召集一个专家工作组，将流行病学和遗传流行病学证据转化为关于这些疾病之间重叠的严格和明确的假设。分析计划遵循GWAS质量控制和荟萃分析的最佳实践，特别是在其对异质性来源的调查方面。统计功效应该上级任何先前的精神病遗传学研究。结果将尽快公布。最后，PGC建议尽可能完全遵守NIH的GWAS数据共享政策，我们提供了详细的数据共享计划和时间表。