Admin Supplement: Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability

管理补充：大规模评估罕见遗传变异对精神症状和认知能力的影响

• 批准号: 10660338
• 负责人: Laura A. Almasy
• 金额: $ 15.4万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-05-06 至 2024-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10660338
• 关键词: Administrative Supplement; All of Us Research Program; Bioinformatics; Biomedical Research; Caring; Cognitive; Communities; Copy Number Polymorphism; Data; Databases; Economics; Electronic Health Record; Encapsulated; Ensure; European; Evaluation; Future; Genes; Genetic Research; Goals; Health; Human Resources; Individual; Link; Machine Learning; Major Mental Illness; Medical; Medical Records; Mental disorders; Methods; Modeling; Mood Disorders; National Institute of Mental Health; Outcome; Participant; Population; Population Heterogeneity; Prevalence; Probability; Psychiatric Diagnosis; Psychopathology; Psychoses; Recurrence; Research; Research Personnel; Research Project Grants; Risk; Sampling; Series; Site; Symptoms; Techniques; Videoconferencing; Work; acronyms; autism spectrum disorder; base; biobank; cognitive ability; cohort; ethnic minority; genetic architecture; genetic variant; genome-wide; health data; improved; indexing; individualized prevention; insight; mathematical model; neuropsychiatric disorder; neuropsychiatry; personalized medicine; psychiatric symptom; racial diversity; racial minority; rare genetic disorder; response; social determinants; socioeconomic diversity; trait; volunteer; whole genome

All of Us Administrative Supplement to Enhance “Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability” U01 MH119690 Supplement Abstract We request an administrative supplement for our 3-site consortium entitled “Large-Scale Evaluation of the Effect of Rare Genetic Variants on Psychiatric Symptoms and Cognitive Ability” U01 MH119690. The supplement will support additional work, planned and performed in our consortium and in conjunction with the larger NIMH Rare Genetic Diseases Network, to advance the primary goal of our network: elucidating the genetic architecture of mental illnesses by studying rare genetic disorders. The goal of our more focused consortium (acronym CAMP for CNVs And Major Psychopathology) is to model the impact of rare and recurrent CNVs on risk for major mental illnesses, related symptoms, and cognitive traits in approximately one million individuals who participated in prior genetics research projects and whose data is shared with the research community. Our administrative supplement, in response to NOT- PM-22-002, will facilitate the inclusion of data from the All of Us Research Program in the CAMP project. Given the racial and socioeconomic diversity in the All of Us cohort, it is critical to include this sample in the CAMP project to ensure generalizability of our findings to all of the U.S. population. The All of Us Research Program aims to advance personalized medicine by accelerating health and medical breakthroughs and enabling individualized prevention, treatment, and care. To that end, All of Us is building a database of one million volunteers who will provide medical records and biosamples to help transform the future of health research by equipping researchers nationwide with expansive health data from diverse populations, especially those underrepresented in biomedical research. To date, data from ~329,000 participants has been collected, with ~50% racial and ethnic minorities and 80% from communities underrepresented in biomedical research overall. Of these initial participants, electronic health record data are available from ~214,200 participants and ~100,000 have sharable whole genome sequence (WGS) data. In a series of video conferences, the CAMP project PIs delineated several critical opportunities for project expansions that would greatly enhance the quality of the results while remaining in line with the initial aims of our project. Thus, the goal of this administrative supplement is to use our validated pipelines to call CNVs in All of Us participants with WGS data (Aim 1) and include these subjects in ongoing CAMP analyses focused on psychopathology (Aim 2) and ancestral diversity (Aim 3). These aims are all activities that are firmly within the scientific scope of work of our original project but require additional bioinformatics and analytical personnel to implement.

我们所有的行政补充剂都可以增强“对罕见的影响的大规模评估 关于精神病症状和认知能力的遗传变异” U01 MH119690 补充摘要 我们要求为我们的三个站点财团的行政补充，标题为“大规模评估 稀有遗传变异对精神症状和认知能力的影响” U01 MH119690。 补充将支持在我们的财团和结合使用的其他工作，计划和执行 随着较大的NIMH罕见遗传疾病网络，可以促进我们网络的主要目标： 通过研究罕见的遗传疾病来阐明精神疾病的遗传结构。目标 我们更集中的财团（CNV和主要心理病理学的首字母缩写训练营）是为了建模 罕见和经常性的CNV对重大精神疾病，相关症状和认知的风险的影响 参与先前遗传学研究项目的大约一百万个人的特征 其数据与研究界共享。我们的行政补充，以回应不 PM-22-002将促进我们所有人在CAMP项目中包含数据的数据。 鉴于我们所有人队列中的种族和社会经济多样性，将此样本包括在 营地项目是为了确保我们的发现对所有美国人口的普遍性。 我们所有的研究计划旨在通过加速健康和 医疗突破并实现个性化的预防，治疗和护理。为此，我们所有人 正在建立一个由一百万志愿者组成的数据库，他们将提供医疗记录和生物样本以帮助 通过为全国范围的研究人员提供广泛的健康数据来改变健康研究的未来 来自潜水员的人群，尤其是生物医学研究中人数不足的人群。迄今为止，来自 已收集约329,000名参与者，种族和少数民族约有50％，从80％ 整体生物医学研究的社区人数不足。在这些初始参与者中，电子 健康记录数据可从约214,200名参与者获得，约有100,000个具有共享的整个基因组 序列（WGS）数据。在一系列视频会议中，CAMP项目PI划定了几个关键 项目扩展的机会，可以极大地提高结果的质量 符合我们项目的最初目标。这是这种行政补充的目的是使用 我们经过验证的管道在我们所有参与者中使用WGS数据（AIM 1）致电CNV，并包括 这些受试者在正在进行的营地分析中，重点是心理病理学（AIM 2）和祖先 多样性（目标3）。这些目的都是所有活动首先在我们的科学范围内 原始项目，但需要其他生物信息学和分析人员才能实施。

项目成果

Phenotypic effects of genetic variants associated with autism.

• DOI: 10.1038/s41591-023-02408-2
• 发表时间: 2023-07
• 期刊: NATURE MEDICINE
• 影响因子: 82.9
• 作者: Rolland, Thomas;Cliquet, Freddy;Anney, Richard J. L.;Moreau, Clara;Traut, Nicolas;Mathieu, Alexandre;Huguet, Guillaume;Duan, Jinjie;Warrier, Varun;Portalier, Swan;Dry, Louise;Leblond, Claire S.;Douard, Elise;Amsellem, Frederique;Malesys, Simon;Maruani, Anna;Toro, Roberto;Borglum, Anders D.;Grove, Jakob;Baron-Cohen, Simon;Packer, Alan;Chung, Wendy K.;Jacquemont, Sebastien;Delorme, Richard;Bourgeron, Thomas
• 通讯作者: Bourgeron, Thomas

Reply to "Comment on: What genes are differentially expressed in individuals with schizophrenia? A systematic review".

回复“评论：精神分裂症个体中哪些基因差异表达？系统评价”。

• DOI: 10.1038/s41380-022-01821-2
• 发表时间: 2023
• 期刊: Molecular psychiatry
• 影响因子: 11
• 作者: Merikangas,AlisonK;Almasy,Laura
• 通讯作者: Almasy,Laura

What genes are differentially expressed in individuals with schizophrenia? A systematic review.

• DOI: 10.1038/s41380-021-01420-7
• 发表时间: 2022-03
• 期刊: MOLECULAR PSYCHIATRY
• 影响因子: 11
• 作者: Merikangas, Alison K.;Shelly, Matthew;Knighton, Alexys;Kotler, Nicholas;Tanenbaum, Nicole;Almasy, Laura
• 通讯作者: Almasy, Laura

Rare and common autism risk variants converge across 16p.

罕见和常见的自闭症风险变异在 16p 期间趋同。

• DOI: 10.1038/s41588-022-01219-4
• 发表时间: 2022
• 期刊: Nature genetics
• 影响因子: 30.8
• 作者: Won,Hyejung;Huguet,Guillaume;Jacquemont,Sébastien
• 通讯作者: Jacquemont,Sébastien

Deletion of Loss-of-Function-Intolerant Genes and Risk of 5 Psychiatric Disorders.

功能丧失不耐受基因的删除和 5 种精神疾病的风险。

• DOI: 10.1001/jamapsychiatry.2021.3211
• 发表时间: 2022
• 期刊: JAMA psychiatry
• 影响因子: 25.8
• 作者: Wainberg,Michael;Merico,Daniele;Huguet,Guillaume;Zarrei,Mehdi;Jacquemont,Sebastien;Scherer,StephenW;Tripathy,ShreejoyJ
• 通讯作者: Tripathy,ShreejoyJ