1/7 PGC: Advancing Discovery and Impact

1/7 PGC：推进发现和影响

• 批准号: 10612491
• 负责人: CYNTHIA M BULIK
• 金额: $ 64.72万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-04-14 至 2026-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10612491
• 关键词: Acceleration; Address; Affect; Alleles; Biological; Biology; Biotechnology; Cells; Clinical; Collaborations; Communication; 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; Investments; Journals; Knowledge; Learning; Life; Maps; Measures; Medical; Medicine; Mendelian randomization; Mental disorders; Meta-Analysis; Methods; Mission; Modeling; Molecular; National Institute of Mental Health; Nature; Neurosciences; Outcome; Paper; Patients; Phase; Phenotype; Productivity; Psychiatric Diagnosis; Psychiatry; Recording of previous events; Reproducibility; Research Personnel; Resistance; Resources; 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 精神病学基因组学联盟成立13年了，它可能是最具创新性和生产力的 精神病学史上最伟大的实验PGC统一了该领域，吸引了一批优秀的 科学家（来自41个国家157个机构的802名调查员）。PGC的工作已经确定了约500个 我们研究的11种精神疾病的基因位点。我们的工作已经产生了320篇论文，其中许多是备受瞩目的 期刊（Nature 3，Cell 5，Science 2，Nat Genet 27，Nat Neurosci 9，Mol Psych 37，Biol Psych 25）。作为 摘要统计数据是免费提供的，精神疾病往往在非PGC的论文中占据突出地位。 investigators.为了推进发现和影响，我们建议继续PGC的工作， 无序群体未来五年将有大量新数据出现。因此，我们可以快速有效地 增加我们对主要精神疾病的基本基础的知识。 目标1：我们将继续在所有工作组中推进严重精神疾病的基因发现， 系统地与大型生物库研究接口，以确保最大的可比性，并积极促进 对来自不同祖先的精神疾病患者进行的新研究，以增加发现和改善 精细映射目的2：大多数研究分析常见变异（目的1）、罕见CNV（目的2）和罕见CNV（目的3）。 单独的外显子组/基因组重新测序结果（通过合作）：我们将应用一个综合框架， 严格评估所有测量类型的遗传变异对精神疾病风险的贡献。 目标3：我们将超越经典的病例对照定义， 通过开展大型跨诊断研究，召集跨学科团队，利用遗传学， 解决有关精神疾病性质的未解决问题，并促进对精神疾病的大规模研究。 在精神病学实践中发现的最常见的病例（利用PGC调查人员的全球影响力）。目标4：我们将 通过翻译努力最大限度地发挥我们工作的影响：与神经科学密切合作 财团了解我们的研究结果的生物学意义;工作，以确定可修改的因果风险 因素;并致力于稳健地预测临床结果并识别患者子集。目标5：提高 我们的工作的影响，通过扩大和正式推广到不同的社区（包括制药和 生物技术），通过数字媒体（Twitter，Facebook，维基百科），并通过开发，分发和更新 为患者、家庭和医疗专业人员提供资源/教育材料。我们将召开一次科学会议， 咨询委员会，以确保我们积极回应那些投资于我们的成果 这项工作的成功完成将极大地推进对精神疾病遗传基础的认识。 具有潜在重大疾病分类学和治疗意义的疾病。这些目标符合一个核心 NIMH的使命，以及PGC的中心思想：将家族史风险因素转化为生物学， 临床和治疗上有意义的见解。