Administrative Supplement: The Clinical Genome Resource - Advancing genomic medicine through biocuration and expert assessment of genes and variants at scale

行政补充：临床基因组资源 - 通过大规模基因和变异的生物管理和专家评估推进基因组医学

• 批准号: 10841906
• 负责人: JONATHAN S BERG
• 金额: $ 39.94万
• 依托单位: UNIV OF NORTH CAROLINA CHAPEL HILL
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-12 至 2026-06-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10841906
• 关键词: Address; Administrative Supplement; American; Area; Clinical; Decision Making; Development; District of Columbia; Funding; Genes; Genetic; Genomic medicine; Genomics; Grant; Health; Health system; Hybrids; Individual; Intervention; Leadership; Medical Genetics; Mendelian disorder; Morbidity - disease rate; National Human Genome Research Institute; Outcome; Persons; Population; Procedures; Research; Science; Variant; Work; cost effectiveness; disorder risk; economic evaluation; ethical, legal, and social implication; evidence base; genome resource; improved; medical schools; meetings; member; mortality; polygenic risk score; poor health outcome; population health; screening; virtual; working group

PROJECT SUMMARY/ABSTRACT In this supplement, we propose two distinct activities focused on the use of genomics in population screening. We will establish a new ClinGen working group to develop an evidence framework to inform decision-making about which targets to include in population screening efforts in unselected populations. We will leverage the expertise and well-established procedures of the ClinGen Actionability Working Group, including recent efforts to develop a new framework for the polygenic risk score (PRS) context. Given that nascent population genomic screening efforts are already in underway in some centers and health systems, this framework development is timely and necessary to provide guidance on conditions that should be considered for screening based on key factors including actionability and cost effectiveness. Overall, this work will significantly contribute to the advancement of genomic medicine at the population scale and provide evidence-based assessments of population health impact for a broad range of end-users. This supplement also requests funds for the UNC team to host and oversee the 2023 annual meeting of the NHGRI Division of Genomic Medicine meeting (GM XV), planned and conducted by the Advisory Council’s Genomic Medicine Working Group. These meetings have historically addressed timely topics in genomic medicine to identify research directions for the field and for NHGRI. The focus of the 2023 meeting will be on genomics and population screening, with meeting objectives aligned with assessing the current state of the science, determining the key challenges and opportunities, and outlining a research agenda. The UNC ClinGen grant is well- suited to help plan this meeting given our close relationship and subcontract with the American College of Medical Genetics and Genomics (ACMG), through which we have coordinated dozens of in-person, virtual, and hybrid Steering Committee meetings and in-person meetings between members of ClinGen’s Clinical Domain Working Groups and Expert Panels.

项目总结/摘要 在本增刊中，我们提出了两个不同的活动，重点是基因组学在 人口普查。 我们将建立一个新的ClinGen工作组，以制定证据框架， 关于哪些目标应纳入人口普查工作的决策 人口。我们将利用ClinGen的专业知识和完善的程序， 工作组，包括最近为制定一个新的 多基因风险评分（PRS）背景。鉴于新生人群基因组筛查工作 一些中心和卫生系统已经在进行中，这一框架的发展是及时的 并有必要提供关于应考虑进行基于筛选的条件的指导 关键因素，包括可操作性和成本效益。总的来说，这项工作将大大 有助于在人口规模上推进基因组医学，并提供 对广泛的最终用户进行人口健康影响的循证评估。 该补充文件还要求提供资金，供研究小组主办和监督2023年年度会议。 NHGRI基因组医学分部会议（GM XV），计划并举行 咨询理事会基因组医学工作组。这些会议在历史上 及时解决了基因组医学的主题，以确定该领域的研究方向， NHGRI。2023年会议的重点将是基因组学和人口筛查， 满足与评估科学现状相一致的目标，确定关键 挑战和机遇，并概述了研究议程。临床基因基金会的拨款- 考虑到我们与美国人的密切关系和友谊， 医学遗传学和基因组学学院（ACMG），通过它，我们已经协调 数十次面对面、虚拟和混合指导委员会会议和面对面会议 ClinGen的临床领域工作组和专家小组成员之间。

项目成果

Reappraisal of Reported Genes for Sudden Arrhythmic Death: Evidence-Based Evaluation of Gene Validity for Brugada Syndrome.

• DOI: 10.1161/circulationaha.118.035070
• 发表时间: 2018-09-18
• 期刊: Circulation
• 影响因子: 37.8
• 作者: Hosseini SM;Kim R;Udupa S;Costain G;Jobling R;Liston E;Jamal SM;Szybowska M;Morel CF;Bowdin S;Garcia J;Care M;Sturm AC;Novelli V;Ackerman MJ;Ware JS;Hershberger RE;Wilde AAM;Gollob MH;National Institutes of Health Clinical Genome Resource Consortium
• 通讯作者: National Institutes of Health Clinical Genome Resource Consortium

Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death.

• DOI: 10.1093/eurheartj/ehab687
• 发表时间: 2022-04-14
• 期刊: EUROPEAN HEART JOURNAL
• 影响因子: 39.3
• 作者: Walsh, Roddy;Adler, Arnon;Amin, Ahmad S.;Abiusi, Emanuela;Care, Melanie;Bikker, Hennie;Amenta, Simona;Feilotter, Harriet;Nannenberg, Eline A.;Mazzarotto, Francesco;Trevisan, Valentina;Garcia, John;Hershberger, Ray E.;Perez, Marco, V;Sturm, Amy C.;Ware, James S.;Zareba, Wojciech;Novelli, Valeria;Wilde, Arthur A. M.;Gollob, Michael H.
• 通讯作者: Gollob, Michael H.

Variant Classification for Pompe disease; ACMG/AMP specifications from the ClinGen Lysosomal Diseases Variant Curation Expert Panel.

庞贝病的变异分类；

• DOI: 10.1016/j.ymgme.2023.107715
• 发表时间: 2023
• 期刊: Molecular genetics and metabolism
• 影响因子: 3.8
• 作者: Goldstein,JenniferL;McGlaughon,Jennifer;Kanavy,Dona;Goomber,Shelly;Pan,Yinghong;Deml,Brett;Donti,Taraka;Kearns,Liz;Seifert,BryceA;Schachter,Miriam;Son,RachelG;Thaxton,Courtney;Udani,Rupa;Bali,Deeksha;Baudet,Heather;Caggana
• 通讯作者: Caggana

Establishing the Medical Actionability of Genomic Variants.

• DOI: 10.1146/annurev-genom-111021-032401
• 发表时间: 2022-08-31
• 期刊: Annual review of genomics and human genetics
• 影响因子: 8.7

ClinGen's Pediatric Actionability Working Group: Clinical actionability of secondary findings from genome-scale sequencing in children and adolescents.

• DOI: 10.1016/j.gim.2022.02.019
• 发表时间: 2022-06
• 期刊: GENETICS IN MEDICINE
• 影响因子: 8.8
• 作者: Hunter, Jessica Ezzell;Jenkins, Charisma L.;Bulkley, Joanna E.;Gilmore, Marian J.;Lee, Kristy;Pak, Christine M.;Wallace, Kathleen E.;Buchanan, Adam H.;Foreman, Ann Katherine M.;Freed, Amanda S.;Goehringer, Scott;Manickam, Kandamurugu;Meeks, Naomi J. L.;Ramos, Erin M.;Shah, Neethu;Steiner, Robert D.;Subramanian, Sai Lakshmi;Trotter, Tracy;Webber, Elizabeth M.;Williams, Marc S.;Goddard, Katrina A. B.;Powell, Bradford C.
• 通讯作者: Powell, Bradford C.