4/7 Psychiatric Genomics Consortium: Advancing Discovery and Impact

4/7 精神病学基因组学联盟：推进发现和影响

• 批准号: 10388089
• 负责人: Caroline M Nievergelt
• 金额: $ 40.89万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-10 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10388089
• 关键词: Address; Affect; Alleles; Biological; Biology; Biotechnology; Cells; Clinical; Collaborations; Communities; Country; DNA Resequencing; Data; Diagnostic; Disease; Educational Materials; Ensure; Epidemiology; Facebook; Family; Fostering; Funding; Genes; Genetic; Genetic Variation; Genets; Genome; Genomics; Goals; Individual; Industry; Institution; Journals; Knowledge; Learning; Life; Measures; Medical; Medicine; Mendelian randomization; Mental disorders; Meta-Analysis; Methods; Mission; Modeling; National Institute of Mental Health; Nature; Neurosciences; Outcome; Paper; Patients; Phase; Phenotype; Psychiatric Diagnosis; Psychiatry; Recording of previous events; Reproducibility; Research Personnel; Resistance; Risk; Risk Factors; Science; Scientist; Source; Symptoms; Therapeutic; Time; Twitter; Update; Variant; Work; base; biobank; career; case control; digital media; education resources; exome; exome sequencing; experimental study; functional genomics; genetic architecture; genetic pedigree; genome sequencing; genome wide association study; genomic data; genomic locus; improved; innovation; insight; instrument; novel; novel therapeutics; outreach; patient stratification; patient subsets; predict clinical outcome; psychiatric genomics; rare variant; severe psychiatric disorder; statistics; success; therapeutic development; translational potential; whole genome; working group

Project Summary Now in its 13th year, the Psychiatric Genomics Consortium is perhaps the most innovative and productive experiment in the history of psychiatry. The PGC unified the field and attracted a cadre of outstanding scientists (802 investigators from 157 institutions in 41 countries). PGC work has led to identification of ~500 genetic loci in the 11 psychiatric disorders we study. Our work has led to 320 papers, many in high-profile journals (Nature 3, Cell 5, Science 2, Nat Genet 27, Nat Neurosci 9, Mol Psych 37, Biol Psych 25). As summary statistics are freely available, psychiatric disorders often feature prominently in papers by non-PGC investigators. To advance discovery and impact, we propose to continue the work of the PGC across 11 disorder groups. Considerable new data are coming in the next five years. We thus can rapidly and efficiently increase our knowledge of the fundamental basis of major psychiatric disorders. Aim 1: we will continue to advance genetic discovery for severe psychiatric disorders in all working groups, systematically interface with large biobank studies to ensure maximal comparability, and aggressively promote new studies of individuals with psychiatric disorders from diverse ancestries to increase discovery and improve fine-mapping. Aim 2: most studies analyze common variation (Aim 1), rare CNV (Aim 2), and rare exome/genome resequencing results (via collaboration) in isolation: we will apply an integrative framework to rigorously evaluate the contributions of all measured types of genetic variation on risk for psychiatric disorders. Aim 3: we will move beyond classical case-control definitions to a more biologically-based and nuanced understanding by enabling large trans-diagnostic studies, convene trans-disciplinary teams to use genetics to address unresolved questions about the nature of psychiatric disorders, and to promote large studies of the severest cases seen in psychiatric practice (leveraging the global reach of PGC investigators). Aim 4: we will work to maximize the impact of our work via translational efforts: close collaborations with neuroscience consortia to understand the biological implications of our findings; work to identify modifiable causal risk factors; and work to robustly predict clinical outcomes and identify patient subsets. Aim 5: we will increase impact of our work by extending and formalizing outreach to different communities (including pharma and biotech), via digital media (Twitter, Facebook, Wikipedia), and by developing, distributing, and updating resources/educational material for patients, families, and medical professionals. We will convene a Scientific Advisory Board to ensure we respond positively to those invested in our results Successful completion of this body of work will greatly advance knowledge of the genetic basis of psychiatric disorders with potentially major nosological and treatment implications. These goals are consistent with a core mission of the NIMH, and the central idea of the PGC: to convert the family history risk factor into biologically, clinically, and therapeutically meaningful insights.

项目摘要 现在是第13年，精神病基因组学联盟也许是最具创新性和富有成效的人 精神病学史上的实验。 PGC统一了该领域，并吸引了一群杰出的干部 科学家（来自41个国家的157个机构的802名调查人员）。 PGC工作导致识别〜500 我们研究的11种精神疾病中的遗传基因座。我们的工作导致了320篇论文，其中许多引人注目 期刊（自然3，细胞5，科学2，NAT Genet 27，Nat Neurosci 9，Mol Psych 37，Biol Psych 25）。作为 摘要统计数据是免费的，精神疾病通常在非PGC的论文中突出显示 调查人员。为了提高发现和影响，我们建议继续在11个中继续PGC的工作 疾病组。在未来五年中，大量新数据将会出现。因此，我们可以迅速有效 提高我们对主要精神疾病基本基础的了解。 目标1：我们将继续推进所有工作组中严重精神疾病的遗传发现， 系统地与大型生物库研究进行接口，以确保最大的可比性，并积极促进 对来自不同祖先精神疾病的人的新研究，以增加发现并改善 精细映射。目标2：大多数研究分析了常见变异（AIM 1），稀有CNV（AIM 2）和罕见 外部/基因组重新陈述结果（通过协作）孤立：我们将应用一个集成框架 严格评估所有测量的遗传变异对精神疾病风险的贡献。 AIM 3：我们将超越经典的病例对照定义，以一种基于生物学的细微差别 通过实现大型的跨诊断研究来理解，召集跨学科团队使用遗传学 解决有关精神疾病性质的未解决的问题，并促进大量研究 在精神病实践中看到的最严重的病例（利用PGC调查人员的全球影响力）。目标4：我们将 通过翻译工作来最大化我们工作的影响：与神经科学的密切合作 了解我们发现的生物学含义；努力确定可修改的因果风险 因素；并努力坚固地预测临床结果并确定患者子集。目标5：我们将增加 通过向不同社区（包括Pharma和包括Pharma和 生物技术），通过数字媒体（Twitter，Facebook，Wikipedia），以及开发，分发和更新 患者，家庭和医疗专业人员的资源/教育材料。我们将召集科学 咨询委员会，以确保我们对投资成果投资的人做出积极回应 成功完成这项工作将大大提高人们对精神病的遗传基础的了解 具有潜在的主要疾病和治疗意义的疾病。这些目标与核心一致 NIMH的使命以及PGC的核心思想：将家族史风险因素转化为生物学， 临床和治疗意义上的见解。