基于人群的队列中基因组结果的返回和总体外显率 (PopSeq)
2026年7月8日 更新者：Robert C. Green, MD, MPH、Brigham and Women's Hospital
PopSeq 项目是一项前瞻性队列研究，将在弗雷明汉心脏研究 (FHS) 和杰克逊心脏研究 (JHS) 队列中开发和实施基因组结果返回 (gRoR) 流程，并探索相关的医学、行为和经济结果。
该研究将解释 JHS/FHS 参与者的基因组序列，这些参与者之前由 TOPMed 测序，他们同意基因组返回结果和/或基因测试。
我们将开发和应用用于基因组变异的可扩展筛选/分类的新方法，并将通过对 FHS 和 JHS 的一部分参与者进行表型分析来探索基因组外显率。
研究概览
详细说明
该项目的目标是：1) 将临床上可操作的基因组结果返回给参与者并跟踪结果。 在同意 gRoR 的活着的 FHS/JHS 参与者中，我们将联系那些在 ACMG 推荐的次要发现列表中指出的基因之一发现有害的可操作变异的人（估计 2% 的参与者）。 2) 改进识别有效致病变异的高通量方法。 改进和应用 FHS/JHS 基因组的高通量筛选方法，以保持高灵敏度检测约 3500 个孟德尔疾病相关基因的有害变异，同时降低非致病性/可能致病性变异的错误发现率。 3) 探索孟德尔疾病的总外显率。 查看来自 FHS 和 JHS 参与者子集的表型数据，并将其与基因型数据进行比较。
要收集的数据包括同意 gRoR 和得知他们在 ACMG 列出的基因之一中具有有害变异的个体的结果和表型数据。 这些数据将通过调查自行报告，并将审查可用的医疗记录。 可以收集和审查其他不可操作的孟德尔疾病基因的其他表型数据，以探索基因组外显率。
被确定在可操作基因中具有有害变异的研究参与者可能会从了解此信息中获得直接的健康益处；然而，将基因组结果返回给未出现医学指征的健康个体可能会造成意想不到的危害，这与筛查和管理中的变异定向增加有关。 本研究的重点是探索与基于人群的队列中返回基因组信息相关的好处和任何潜在危害。 它还将使我们能够更好地了解这些变异在未选择疾病状态的两个人群中的外显率，并使我们能够比较主要是非裔美国人人群与高加索人群的结果。 开发简化变异分析的方法将有助于提高实验室效率，并将推动变异管理和分析领域的发展。
研究类型
介入性
注册 (实际的)
7603
阶段
- 不适用
联系人和位置
本节提供了进行研究的人员的详细联系信息，以及有关进行该研究的地点的信息。
学习地点
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Massachusetts
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Framingham、Massachusetts、美国、01702
- Framingham Heart Study
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Mississippi
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Jackson、Mississippi、美国、39213
- Jackson Heart Study
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参与标准
研究人员寻找符合特定描述的人，称为资格标准。这些标准的一些例子是一个人的一般健康状况或先前的治疗。
资格标准
适合学习的年龄
18年 至 100年 (成人、年长者)
接受健康志愿者
不
描述
纳入标准：
- 参与 Framingham 心脏研究和 Jackson 心脏研究的在世个体已将其基因组测序作为 TOPMed 计划的一部分。
- 18岁以上的成年人
- 同意将其 DNA 样本用于研究目的的人（以及参与 gRoR 并同意接收基因组信息的人）。
排除标准：
- Framingham Heart Study 或 Jackson Heart Study 的参与者尚未将其基因组测序作为 TOPMed 的一部分
- 没有选择基因组/遗传研究的参与者
- 同意/不同意接受基因组结果的参与者（仅针对本研究的 gRoR 部分）
学习计划
本节提供研究计划的详细信息，包括研究的设计方式和研究的衡量标准。
研究是如何设计的？
设计细节
- 主要用途：预防
- 分配：不适用
- 介入模型：单组作业
- 屏蔽：无（打开标签）
武器和干预
参与者组/臂 |
干预/治疗 |
|---|---|
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实验性的：具有可操作基因组发现的 FHS 和 JHS 参与者
如果 ACMG v2.0 基因中的可操作遗传结果被识别，并且将有机会通过该研究对他们的研究结果进行临床确认，那么 Framingham 和 Jackson 心脏研究参与者的基因组测序将作为 TOPMed 的一部分进行。
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全基因组测序和 ACMG 二级发现列表中包含的基因的可操作基因组结果报告。
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研究衡量的是什么？
主要结果指标
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Follow Through With Disclosure
大体时间：From genetic result notification to 8 months post-disclosure
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Living JHS/FHS participants sequenced as part of the TOPMed program who were notified about an actionable genetic result that warranted having the research result verified who followed through with having their result confirmed and disclosed to their health care provider.
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From genetic result notification to 8 months post-disclosure
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Total Costs of Program Implementation
大体时间：From the initiation of bioinformatics analysis to disclosure of confirmed actionable genetic finding (approximately 6 months).
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We will determine the costs and associated time demands of implementing gRoR using a microcosting approach in which study staff track the amount of time they spend and the resources they use for each step of the protocol.
Ranges are based on 50% to 200% of point estimates given variability in wages and prices of services.
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From the initiation of bioinformatics analysis to disclosure of confirmed actionable genetic finding (approximately 6 months).
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Costs of Follow-Up Care
大体时间：1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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For follow-up medical care, we use a gross costing approach where we apply Centers for Medicare and Medicaid fee schedules to participant-reported referrals and tests.
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1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Guideline Compliance
大体时间：At the time of disclosure of confirmed findings (approximately 3 months after initial results notification)
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Number of participants with actionable genetic results who, per the judgement of a genetic specialist, had already met clinical criteria for genetic testing based on their personal and family histories of disease.
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At the time of disclosure of confirmed findings (approximately 3 months after initial results notification)
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New and Modified Diagnoses
大体时间：6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results);1 Year Post-Disclosure Survey (from 1 year to 15 months after disclosure of confirmed results)
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We will examine cases to determine the percentage of individuals who report a new or modified diagnosis attributed to results disclosure.
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6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results);1 Year Post-Disclosure Survey (from 1 year to 15 months after disclosure of confirmed results)
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Self-Rated Health
大体时间：Post Disclosure Survey (up to 1 month from disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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A single item of self rated health derived from the SF-12v2.
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Post Disclosure Survey (up to 1 month from disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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Number of Participants With Recommendations to Referrals or Services During Clinical Disclosure Sessions
大体时间：From disclosure to 1 month post-disclosure
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We reviewed chart notes from results disclosure sessions to determine whether referrals or services were recommended in response to genetic findings.
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From disclosure to 1 month post-disclosure
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Health Care Utilization
大体时间：1 year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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Health care utilization in response to results disclosure reported by participants in the one year follow-up survey, including referrals, tests and/or procedures, and changes to medications.
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1 year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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其他结果措施
结果测量 |
措施说明 |
大体时间 |
|---|---|---|
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Self-Reported Changes to Health Behaviors
大体时间：1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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A series of standardized yes/no questions that assess whether disclosed genetic information motivated participants to make changes to health behaviors, including diet, exercise, dietary supplements use, alcohol use, stress management, and smoking.
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1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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Disclosure-specific Impact
大体时间：6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results)
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The survey assessed the disclosure-specific impact of information on distress and positive emotions using an adapted 12-item version of the FaCTOR, a validated instrument developed for genomic sequencing that is sensitive to responses to high- and low-risk genetic risk results.
Subscales assess negative emotions (range: 3 to 15), positive feelings (reverse-scored, range: 4 to 20), uncertainty (range: 3 to 15), and privacy concerns (range: 2 to 10), with higher scores on each subscale indicating more negative experiences.
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6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results)
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Satisfaction With Disclosure
大体时间：6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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Surveys assessed how helpful participants felt the results disclosure session was using a novel single question.
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6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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Decisional Regret
大体时间：6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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Surveys assessed if participants regretted their decisions to receive their genetic findings using a novel single question.
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6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results); 1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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Sharing With Relatives
大体时间：1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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The survey assessed with whether participants shared their genetic information with relatives .
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1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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Family Testing
大体时间：1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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The survey assessed whether participants had relatives that received genetic testing based on disclosure to the participant.
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1 Year Post-Disclosure Survey (from 12 months to 15 months after disclosure of confirmed results)
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General Anxiety
大体时间：Post Disclosure Survey (up to 1 month from disclosure of confirmed results); 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results)
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We measure general anxiety using a 4-item version of the General Anxiety Disorder Scale, a validated scale that allows investigators to identify individuals with a potential mood disorder.
Scores range from 4 to 16, with higher scores indicating greater anxiety.
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Post Disclosure Survey (up to 1 month from disclosure of confirmed results); 6 months Post-Disclosure Survey (6-9 months after disclosure of confirmed results)
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合作者和调查者
在这里您可以找到参与这项研究的人员和组织。
出版物和有用的链接
负责输入研究信息的人员自愿提供这些出版物。这些可能与研究有关。
一般刊物
- Wolf SM, Branum R, Koenig BA, Petersen GM, Berry SA, Beskow LM, Daly MB, Fernandez CV, Green RC, LeRoy BS, Lindor NM, O'Rourke PP, Breitkopf CR, Rothstein MA, Van Ness B, Wilfond BS. Returning a Research Participant's Genomic Results to Relatives: Analysis and Recommendations. J Law Med Ethics. 2015 Fall;43(3):440-63. doi: 10.1111/jlme.12288.
- Wolf SM, Lawrenz FP, Nelson CA, Kahn JP, Cho MK, Clayton EW, Fletcher JG, Georgieff MK, Hammerschmidt D, Hudson K, Illes J, Kapur V, Keane MA, Koenig BA, Leroy BS, McFarland EG, Paradise J, Parker LS, Terry SF, Van Ness B, Wilfond BS. Managing incidental findings in human subjects research: analysis and recommendations. J Law Med Ethics. 2008 Summer;36(2):219-48, 211. doi: 10.1111/j.1748-720X.2008.00266.x.
- Vassy JL, Lautenbach DM, McLaughlin HM, Kong SW, Christensen KD, Krier J, Kohane IS, Feuerman LZ, Blumenthal-Barby J, Roberts JS, Lehmann LS, Ho CY, Ubel PA, MacRae CA, Seidman CE, Murray MF, McGuire AL, Rehm HL, Green RC; MedSeq Project. The MedSeq Project: a randomized trial of integrating whole genome sequencing into clinical medicine. Trials. 2014 Mar 20;15:85. doi: 10.1186/1745-6215-15-85.
- McLaughlin HM, Ceyhan-Birsoy O, Christensen KD, Kohane IS, Krier J, Lane WJ, Lautenbach D, Lebo MS, Machini K, MacRae CA, Azzariti DR, Murray MF, Seidman CE, Vassy JL, Green RC, Rehm HL; MedSeq Project. A systematic approach to the reporting of medically relevant findings from whole genome sequencing. BMC Med Genet. 2014 Dec 14;15:134. doi: 10.1186/s12881-014-0134-1.
- Vassy JL, Christensen KD, Schonman EF, Blout CL, Robinson JO, Krier JB, Diamond PM, Lebo M, Machini K, Azzariti DR, Dukhovny D, Bates DW, MacRae CA, Murray MF, Rehm HL, McGuire AL, Green RC; MedSeq Project. The Impact of Whole-Genome Sequencing on the Primary Care and Outcomes of Healthy Adult Patients: A Pilot Randomized Trial. Ann Intern Med. 2017 Jun 27;167(3):159-169. doi: 10.7326/M17-0188. Print 2017 Aug 1.
- Christensen KD, Vassy JL, Phillips KA, Blout CL, Azzariti DR, Lu CY, Robinson JO, Lee K, Douglas MP, Yeh JM, Machini K, Stout NK, Rehm HL, McGuire AL, Green RC, Dukhovny D; MedSeq Project. Short-term costs of integrating whole-genome sequencing into primary care and cardiology settings: a pilot randomized trial. Genet Med. 2018 Dec;20(12):1544-1553. doi: 10.1038/gim.2018.35. Epub 2018 Mar 22.
- Lupo PJ, Robinson JO, Diamond PM, Jamal L, Danysh HE, Blumenthal-Barby J, Lehmann LS, Vassy JL, Christensen KD, Green RC, McGuire AL; MedSeq Project team. Patients' perceived utility of whole-genome sequencing for their healthcare: findings from the MedSeq project. Per Med. 2016 Jan 1;13(1):13-20. doi: 10.2217/pme.15.45. Epub 2016 Jan 8.
- Biesecker LG, Green RC. Diagnostic clinical genome and exome sequencing. N Engl J Med. 2014 Sep 18;371(12):1170. doi: 10.1056/NEJMc1408914. No abstract available.
- Wolf SM, Crock BN, Van Ness B, Lawrenz F, Kahn JP, Beskow LM, Cho MK, Christman MF, Green RC, Hall R, Illes J, Keane M, Knoppers BM, Koenig BA, Kohane IS, Leroy B, Maschke KJ, McGeveran W, Ossorio P, Parker LS, Petersen GM, Richardson HS, Scott JA, Terry SF, Wilfond BS, Wolf WA. Managing incidental findings and research results in genomic research involving biobanks and archived data sets. Genet Med. 2012 Apr;14(4):361-84. doi: 10.1038/gim.2012.23.
- Burke W, Evans BJ, Jarvik GP. Return of results: ethical and legal distinctions between research and clinical care. Am J Med Genet C Semin Med Genet. 2014 Mar;166C(1):105-11. doi: 10.1002/ajmg.c.31393. Epub 2014 Mar 10.
- National Heart, Lung, and Blood Institute working group; Fabsitz RR, McGuire A, Sharp RR, Puggal M, Beskow LM, Biesecker LG, Bookman E, Burke W, Burchard EG, Church G, Clayton EW, Eckfeldt JH, Fernandez CV, Fisher R, Fullerton SM, Gabriel S, Gachupin F, James C, Jarvik GP, Kittles R, Leib JR, O'Donnell C, O'Rourke PP, Rodriguez LL, Schully SD, Shuldiner AR, Sze RK, Thakuria JV, Wolf SM, Burke GL. Ethical and practical guidelines for reporting genetic research results to study participants: updated guidelines from a National Heart, Lung, and Blood Institute working group. Circ Cardiovasc Genet. 2010 Dec;3(6):574-80. doi: 10.1161/CIRCGENETICS.110.958827.
- Natarajan P, Gold NB, Bick AG, McLaughlin H, Kraft P, Rehm HL, Peloso GM, Wilson JG, Correa A, Seidman JG, Seidman CE, Kathiresan S, Green RC. Aggregate penetrance of genomic variants for actionable disorders in European and African Americans. Sci Transl Med. 2016 Nov 9;8(364):364ra151. doi: 10.1126/scitranslmed.aag2367.
- Christensen KD, Phillips KA, Green RC, Dukhovny D. Cost Analyses of Genomic Sequencing: Lessons Learned from the MedSeq Project. Value Health. 2018 Sep;21(9):1054-1061. doi: 10.1016/j.jval.2018.06.013. Epub 2018 Aug 14.
- Roberts JS, Robinson JO, Diamond PM, Bharadwaj A, Christensen KD, Lee KB, Green RC, McGuire AL; MedSeq Project team. Patient understanding of, satisfaction with, and perceived utility of whole-genome sequencing: findings from the MedSeq Project. Genet Med. 2018 Sep;20(9):1069-1076. doi: 10.1038/gim.2017.223. Epub 2018 Jan 4.
- Christensen KD, Dukhovny D, Siebert U, Green RC. Assessing the Costs and Cost-Effectiveness of Genomic Sequencing. J Pers Med. 2015 Dec 10;5(4):470-86. doi: 10.3390/jpm5040470.
- Machini K, Ceyhan-Birsoy O, Azzariti DR, Sharma H, Rossetti P, Mahanta L, Hutchinson L, McLaughlin H; MedSeq Project; Green RC, Lebo M, Rehm HL. Analyzing and Reanalyzing the Genome: Findings from the MedSeq Project. Am J Hum Genet. 2019 Jul 3;105(1):177-188. doi: 10.1016/j.ajhg.2019.05.017. Epub 2019 Jun 27.
- Green RC, Berg JS, Grody WW, Kalia SS, Korf BR, Martin CL, McGuire AL, Nussbaum RL, O'Daniel JM, Ormond KE, Rehm HL, Watson MS, Williams MS, Biesecker LG; American College of Medical Genetics and Genomics. ACMG recommendations for reporting of incidental findings in clinical exome and genome sequencing. Genet Med. 2013 Jul;15(7):565-74. doi: 10.1038/gim.2013.73. Epub 2013 Jun 20.
- Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, Herman GE, Hufnagel SB, Klein TE, Korf BR, McKelvey KD, Ormond KE, Richards CS, Vlangos CN, Watson M, Martin CL, Miller DT. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med. 2017 Feb;19(2):249-255. doi: 10.1038/gim.2016.190. Epub 2016 Nov 17.
研究记录日期
这些日期跟踪向 ClinicalTrials.gov 提交研究记录和摘要结果的进度。研究记录和报告的结果由国家医学图书馆 (NLM) 审查，以确保它们在发布到公共网站之前符合特定的质量控制标准。
研究主要日期
学习开始 (实际的)
2021年6月9日
初级完成 (实际的)
2025年5月30日
研究完成 (实际的)
2025年5月30日
研究注册日期
首次提交
2019年12月10日
首先提交符合 QC 标准的
2019年12月10日
首次发布 (实际的)
2019年12月12日
研究记录更新
最后更新发布 (实际的)
2026年8月3日
上次提交的符合 QC 标准的更新
2026年7月8日
最后验证
2026年7月1日
更多信息
与本研究相关的术语
其他相关的 MeSH 术语
其他研究编号
- R01HL143295 (美国 NIH 拨款/合同)
计划个人参与者数据 (IPD)
计划共享个人参与者数据 (IPD)？
不
IPD 计划说明
不会共享个人参与者数据。
汇总数据将通过出版物共享，并将根据要求予以考虑。
药物和器械信息、研究文件
研究美国 FDA 监管的药品
不
研究美国 FDA 监管的设备产品
不
此信息直接从 clinicaltrials.gov 网站检索，没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求，请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改，我们的网站上也会自动更新.