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.

全民美行政补充提升“大规模效果评估” 精神症状和认知能力的遗传变异”U 01 MH 119690 补充摘要 我们要求为我们的三个地点联合体提供一份题为“大规模评估 罕见遗传变异对精神症状和认知能力的影响”U 01 MH 119690。的 补充将支持在我们的联合体中计划和执行的额外工作， 与更大的NIMH罕见遗传疾病网络合作，推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。的目标 我们更集中的联盟（CNVs和主要精神病理学的缩写CAMP）是模拟 罕见和复发性CNVs对主要精神疾病风险、相关症状和认知功能的影响 参与先前遗传学研究项目的大约100万人的特征， 其数据与研究社区共享。我们的行政补充，在回应不- PM-22-002，将促进从我们所有的研究计划在CAMP项目的数据纳入。 考虑到“我们所有人”群体的种族和社会经济多样性，将这一样本纳入 CAMP项目，以确保我们的研究结果对所有美国人的普遍性。 All of Us研究计划旨在通过加速健康和健康， 医学突破，实现个性化预防、治疗和护理。为此，我们所有人 正在建立一个由100万志愿者组成的数据库，这些志愿者将提供医疗记录和生物样本， 通过为全国的研究人员提供广泛的健康数据，改变健康研究的未来 来自不同的人群，特别是那些在生物医学研究中代表性不足的人群。迄今为止， 收集了约329，000名参与者，其中约50%为少数民族和少数民族，80%来自 在生物医学研究中总体代表性不足的社区。在这些最初的参与者中，电子 可从约214，200名参与者获得健康记录数据，其中约100，000人具有可共享的全基因组 序列（WGS）数据。在一系列视频会议中，CAMP项目PI描述了几个关键的 扩大项目的机会，这将大大提高成果的质量，同时保持 符合我们项目的最初目标。因此，这一行政补充的目标是利用 我们经过验证的管道，可以使用WGS数据调用All of Us参与者中的CNV（目标1），包括 这些正在进行的CAMP分析的受试者集中在精神病理学（目标2）和祖先 多样性（目标3）。这些目标都是在我们的科学工作范围内的活动。 原始项目，但需要额外的生物信息学和分析人员来实施。

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

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

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