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 现在已经是第13个年头了，精神病学基因组学联盟可能是最具创新性和生产力的 精神病学史上的实验。PGC统一了整个领域，吸引了一批优秀的 科学家(来自41个国家157个机构的802名调查人员)。PGC的工作已经确定了~500人 我们研究的11种精神障碍中的遗传基因。我们的工作已经产生了320篇论文，其中许多都是高调的 期刊(自然3，细胞5，科学2，NAT基因27，NAT神经科学9，摩尔心理学37，生物心理学25)。AS 摘要统计数据是免费提供的，精神障碍经常出现在非PGC的论文中 调查人员。为了促进发现和影响，我们建议在11个月内继续PGC的工作 有障碍的群体。在接下来的五年里，将会有大量的新数据。因此，我们可以快速而高效地 增加我们对重大精神障碍的基本基础的认识。 目标1：我们将继续在所有工作组推进严重精神障碍的基因发现， 系统地与大型生物库研究对接，以确保最大的可比性，并积极推动 对不同祖先精神障碍患者的新研究，以增加发现和改进 精细映射。目标2：大多数研究分析常见变异(目标1)、罕见CNV(目标2)和罕见 孤立的外显子组/基因组重测序结果(通过合作)：我们将应用一个综合框架来 严格评估所有可测量类型的基因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，转向更具生物学基础和细微差别的 通过启用大型跨诊断研究来理解，召集跨学科团队利用遗传学 解决有关精神障碍本质的悬而未决的问题，并促进对 最严重的案例出现在精神病学实践中(利用PGC调查人员的全球影响力)。目标4：我们将 努力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 财团了解我们发现的生物学影响；努力确定可改变的因果风险 因素；并致力于强有力地预测临床结果和确定患者亚群。目标5：我们将增加 通过将外展扩展到不同的社区并将其正规化，对我们的工作产生影响(包括制药和 生物技术)，通过数字媒体(Twitter、Facebook、维基百科)，以及通过开发、分发和更新 为患者、家属和医疗专业人员提供的资源/教育材料。我们将召开一次科学会议 咨询委员会，以确保我们对那些投资于我们结果的人做出积极回应 这项工作的成功完成将极大地促进对精神疾病遗传基础的了解 具有潜在的重大病因学和治疗影响的疾病。这些目标与一个核心是一致的 NIMH的使命和PGC的中心思想：将家族史风险因素转化为生物学因素， 在临床上和治疗上有意义的见解。