CNV And Stroke (CaNVAS)
CNV 和中风 (CaVAS)
基本信息
- 批准号:10308412
- 负责人:
- 金额:$ 50.73万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2020
- 资助国家:美国
- 起止时间:2020-03-01 至 2024-11-30
- 项目状态:已结题
- 来源:
- 关键词:AddressAdultAffectAfricanAgeBioinformaticsBiologicalBiological MarkersBloodBlood PressureCardiovascular systemCause of DeathCoagulation ProcessComplexCopy Number PolymorphismDataData SetDetectionDiseaseDrug TargetingEthnic OriginEtiologyEuropeanFunctional disorderGenesGeneticGenetic studyGenotypeHeritabilityInflammationInterdisciplinary StudyInternationalIschemic StrokeLeadershipLondonManualsMeasuresMessenger RNAMethodologyMethylationMicroRNAsMorbidity - disease rateOutcomePathway interactionsPhenotypePopulationPositioning AttributePredispositionPreventionProteomicsRNAResearchResearch PersonnelResourcesRiskRisk FactorsRoleStrokeStroke preventionSusceptibility GeneSwedenSyndromeTrainingTrans-Omics for Precision MedicineTreatment outcomeUnited StatesVariantWomanbasecase controlcausal variantcirculating biomarkerscostcost efficientdisabilityethnic diversityexomeexperiencegenome wide association studygenome-wideimprovedinsightmenmetabolomicsmortalitynovelprogramssexstroke outcomestroke risktool
项目摘要
Ischemic stroke is the 4th leading cause of death in the U.S. and a major cause of disability. The etiology
of stroke is multifactorial and poorly understood. Genetics is a potentially powerful tool for better understanding
disease etiology as it can highlight biological mechanisms underlying disease and point the way to improved
prevention, treatment, and outcome. Large genome-wide association studies (GWAS) of ischemic stroke (IS)
populations have been successful at identifying stroke-risk-associated loci with small effect sizes, however,
the role of copy number variation (CNV) variation in stroke susceptibility has yet to be explored, and is the
premise of our proposal. Studying CNV has revealed important insights for numerous other complex diseases.
Further, we recently demonstrated that a higher CNV burden genome-wide is associated with poorer stroke
outcome at 3 months. We therefore hypothesize that CNV analyses of existing GWAS and exome data will be
a highly effective and cost-efficient methodology to identify novel associations illuminating stroke mechanisms,
treatment targets, and outcome drivers. We further speculate that these analyses will identify CNVs of large
effect size in ischemic stroke, as suggested by the existence of numerous monogenic, syndromic and complex
diseases associated with CNV and that CNV may help explain the ‘missing heritability’ known to exist in stroke.
For this application, we have already assembled over 24,500 well-phenotyped IS cases, including IS
subtypes, and over 43,500 controls, all with readily available genotyping on GWAS and exome arrays, with
case measures of stroke outcome. To evaluate CNV-associated stroke risk and stroke outcome we will: 1)
perform Risk Discovery using several analytic approaches to identify CNVs that are associated with the risk of
IS and its subtypes, across the age-, sex- and ethnicity-spectrums; 2) perform Risk Replication and Extension
to determine whether the identified stroke-associated CNVs replicate in the ethnically diverse TOPMed
Consortia and then using existing TOPMed and GeneStroke Consortium biomarker data (e.g. methylation,
proteomic, RNA, miRNA, etc.) evaluate how the identified CNVs exert their effects on stroke risk, and lastly;
3) perform outcome-based Replication and Extension analyses of our recent findings demonstrating an inverse
relationship between CNV burden and stroke outcome at 3 months (mRS) in these additional datasets, and
then determine the key CNV drivers responsible for these associations using existing biomarker data.
Our study will leverage the numerous advantages of using existing case-control data sets, exploring the
relationships between CNV and IS and its subtypes, and outcome at 3 months, across the sex-, age- and
ethnicity-spectrums. The proposed study creates a new training network for junior investigators and establishes
a unique resource for the continued study of the genetic basis of IS. The successful identification of novel
genes, pathways and drug targets has the potential to transform our understanding of the stroke
pathophysiology leading to more effective prevention, treatment and outcome strategies.
缺血性中风是美国第四大死亡原因,也是残疾的主要原因。病因
中风的发生是多因素的,而且人们对此知之甚少。遗传学是一个潜在的强大工具,
疾病病因学,因为它可以突出疾病的生物学机制,并指出改善
预防、治疗和结果。缺血性卒中(IS)的大型全基因组关联研究(GWAS)
人群已经成功地鉴定了具有小效应大小的中风风险相关基因座,然而,
拷贝数变异(CNV)变异在中风易感性中的作用还有待研究,
我们提案的前提。研究CNV揭示了许多其他复杂疾病的重要见解。
此外,我们最近证实,较高的CNV基因组负荷与较差的中风有关
3个月的结果。因此,我们假设,现有的GWAS和外显子组数据的CNV分析将是一个新的研究方向。
一种高度有效和成本有效的方法来识别阐明中风机制的新关联,
治疗目标和结果驱动因素。我们进一步推测,这些分析将确定大的CNVs。
缺血性卒中的效应量,如存在许多单基因、综合征和复杂的
CNV可能有助于解释已知存在于中风中的“缺失遗传性”。
对于这个应用,我们已经收集了超过24,500个表型良好的IS病例,包括IS
亚型和超过43,500个对照,所有这些都在GWAS和外显子组阵列上进行了基因分型,
卒中结局的病例测量。为了评估CNV相关的卒中风险和卒中结局,我们将:1)
使用几种分析方法进行风险发现,以识别与以下风险相关的CNV
IS及其亚型,跨越年龄、性别和种族谱; 2)进行风险复制和扩展
为了确定所鉴定的中风相关CNV是否在种族多样性TOPM中复制,
Consortia,然后使用现有的TOPMed和GeneStroke Consortia生物标志物数据(例如甲基化,
蛋白质组学、RNA、miRNA等)评估所识别的CNV如何对中风风险产生影响,最后;
3)对我们最近的研究结果进行基于结果的复制和扩展分析,证明了
在这些额外数据集中,CNV负荷与3个月时卒中结局(mRS)之间的关系,以及
然后使用现有的生物标志物数据确定负责这些关联的关键CNV驱动因素。
我们的研究将利用现有病例对照数据集的众多优势,探索
CNV和IS及其亚型之间的关系,以及3个月时的结果,跨性别,年龄和
种族光谱拟议的研究为初级调查员建立了一个新的培训网络,
一个独特的资源,为继续研究遗传基础的IS。小说的成功鉴定
基因、通路和药物靶点有可能改变我们对中风的理解,
病理生理学导致更有效的预防,治疗和结果策略。
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
数据更新时间:{{ journalArticles.updateTime }}
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
数据更新时间:{{ journalArticles.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ monograph.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ sciAawards.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ conferencePapers.updateTime }}
{{ item.title }}
- 作者:
{{ item.author }}
数据更新时间:{{ patent.updateTime }}
JOHN W. COLE其他文献
JOHN W. COLE的其他文献
{{
item.title }}
{{ item.translation_title }}
- DOI:
{{ item.doi }} - 发表时间:
{{ item.publish_year }} - 期刊:
- 影响因子:{{ item.factor }}
- 作者:
{{ item.authors }} - 通讯作者:
{{ item.author }}
{{ truncateString('JOHN W. COLE', 18)}}的其他基金
Whole Exome Sequencing Study of Early-Onset Ischemic Stroke
早发性缺血性中风的全外显子组测序研究
- 批准号:
10514591 - 财政年份:2020
- 资助金额:
$ 50.73万 - 项目类别:
Whole Exome Sequencing Study of Early-Onset Ischemic Stroke
早发性缺血性中风的全外显子组测序研究
- 批准号:
10293528 - 财政年份:2020
- 资助金额:
$ 50.73万 - 项目类别:
相似海外基金
Co-designing a lifestyle, stop-vaping intervention for ex-smoking, adult vapers (CLOVER study)
为戒烟的成年电子烟使用者共同设计生活方式、戒烟干预措施(CLOVER 研究)
- 批准号:
MR/Z503605/1 - 财政年份:2024
- 资助金额:
$ 50.73万 - 项目类别:
Research Grant
Early Life Antecedents Predicting Adult Daily Affective Reactivity to Stress
早期生活经历预测成人对压力的日常情感反应
- 批准号:
2336167 - 财政年份:2024
- 资助金额:
$ 50.73万 - 项目类别:
Standard Grant
RAPID: Affective Mechanisms of Adjustment in Diverse Emerging Adult Student Communities Before, During, and Beyond the COVID-19 Pandemic
RAPID:COVID-19 大流行之前、期间和之后不同新兴成人学生社区的情感调整机制
- 批准号:
2402691 - 财政年份:2024
- 资助金额:
$ 50.73万 - 项目类别:
Standard Grant
Migrant Youth and the Sociolegal Construction of Child and Adult Categories
流动青年与儿童和成人类别的社会法律建构
- 批准号:
2341428 - 财政年份:2024
- 资助金额:
$ 50.73万 - 项目类别:
Standard Grant
Elucidation of Adult Newt Cells Regulating the ZRS enhancer during Limb Regeneration
阐明成体蝾螈细胞在肢体再生过程中调节 ZRS 增强子
- 批准号:
24K12150 - 财政年份:2024
- 资助金额:
$ 50.73万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Understanding how platelets mediate new neuron formation in the adult brain
了解血小板如何介导成人大脑中新神经元的形成
- 批准号:
DE240100561 - 财政年份:2024
- 资助金额:
$ 50.73万 - 项目类别:
Discovery Early Career Researcher Award
Laboratory testing and development of a new adult ankle splint
新型成人踝关节夹板的实验室测试和开发
- 批准号:
10065645 - 财政年份:2023
- 资助金额:
$ 50.73万 - 项目类别:
Collaborative R&D
Usefulness of a question prompt sheet for onco-fertility in adolescent and young adult patients under 25 years old.
问题提示表对于 25 岁以下青少年和年轻成年患者的肿瘤生育力的有用性。
- 批准号:
23K09542 - 财政年份:2023
- 资助金额:
$ 50.73万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Identification of new specific molecules associated with right ventricular dysfunction in adult patients with congenital heart disease
鉴定与成年先天性心脏病患者右心室功能障碍相关的新特异性分子
- 批准号:
23K07552 - 财政年份:2023
- 资助金额:
$ 50.73万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Issue identifications and model developments in transitional care for patients with adult congenital heart disease.
成人先天性心脏病患者过渡护理的问题识别和模型开发。
- 批准号:
23K07559 - 财政年份:2023
- 资助金额:
$ 50.73万 - 项目类别:
Grant-in-Aid for Scientific Research (C)