Channelopathies and Cardiomyopathies Among Sudden Deaths in the Young
Channelopathies and Cardiomyopathies Among Sudden Deaths in the Young
批准号:
9242061
负责人:
Alfred L. George
金额:
$82.9万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-04-01 至 2020-03-31
关键词:
Absence EpilepsyAgeArrhythmiaAutopsyBioinformaticsCardiacCardiomyopathiesCessation of lifeChicagoChildClinical DataCodeCollaborationsComputer SimulationCongenital cardiomyopathyCosts and BenefitsCounselingCountyCoupledDNADataData AnalysesDepositionDrug ExposureElectrophysiology (science)EnsureEpilepsyEtiologyEventExposure toFamilyFamily memberFirst Degree RelativeFrequenciesFutureGene FrequencyGeneral PopulationGenesGeneticGenetic Predisposition to DiseaseGoldHeart DiseasesHereditary DiseaseHuman GenomeIllinoisIncidenceInheritedIon ChannelLaboratoriesLifeLong QT SyndromeMedical ExaminersMolecularMutationMyocardialParentsPathogenesisPathogenicityPersonsPharmacologyPopulation ControlPredispositionPrevalenceProbabilityPropertyProtocols documentationPublic HealthRegistriesResearchResearch DesignResourcesRiskSchemeSudden DeathTestingVariantWorkcase controlcookingdata registrydesignexome sequencingexperimental studygenetic variantgenome sequencinggenomic dataheart rhythminnovationnext generation sequencingnovelpublic health relevanceresearch studyscreeningsupercomputervariant of unknown significancewhole genomeyoung adult
中文摘要
英文摘要
DESCRIPTION (provided by applicant): Sudden unexplained death (SUD) is a tragic event at any age. The incidence of SUD between the ages of 1 and 35 years is 1-3 events per 100,000 person-years. In addition to loss of life, SUD may herald increased risk for sudden death in surviving first-degree relatives. Genetic disorders of heart rhythm (e.g., channelopathies) and myocardial function (e.g., cardiomyopathies) are blamed for approximately 25% of SUD cases. Screening first-degree relatives of a SUD victim for genetic disease may identify additional family members at risk for sudden death. We propose a three-tiered research study designed to uncover the prevalence and mutational spectrum of channelopathies and cardiomyopathies among cases of sudden death collected by the Sudden Death in the Young (SDY) Case Registry that occur in the absence of epilepsy and have a high likelihood of having a cardiac etiology. In Specific Aim 1, we propose to perform whole genome sequencing of 500 SDY cases coupled with targeted bioinformatics analysis of genes with known involvement in congenital arrhythmia susceptibilities or inherited cardiomyopathies. Whole genome sequencing yields more uniform coverage of coding sequences than exome sequencing and offers opportunities to enable studies of analysis of noncoding variation. In Specific Aim 2, we propose to perform experiments to elucidate the functional consequences of SDY-associated genetic variants in cardiac ion channel genes, especially SCN5A, KCNQ1 and KCNH2. These experiments will generate data essential for assigning the likelihood of pathogenicity for a large class of anticipated variants predisposing to SUD. Finally, In Specific Aim 3, we will determine the frequency with which pathogenic variants in genes associated with congenital arrhythmia susceptibility and cardiomyopathy are inherited from a parent rather than arising de novo. Ascertaining the rate of transmitted versus de novo mutations in SUD cases has important implications for public health and family counseling. As part of our experimental plan, we will also identify new SDY cases through our existing collaboration with Medical Examiner's Offices in Chicago and surrounding counties in Illinois, thereby adding value to the registry and ensuring robust accrual of SDY cases that can be shared across the research network.
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会议论文
Northwestern University O'Brien Kidney National Resource Center
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批准号:10754080
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项目类别:
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资助金额:$99.21万
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财政年份:2023
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负责人:Alfred L. George
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依托单位:
Cellular Pathophysiology of Neuronal Na/K-ATPase Dysfunction
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批准号:10539624
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项目类别:
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资助金额:$40.0万
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财政年份:2022
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负责人:Alfred L. George
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依托单位:
Cellular Pathophysiology of Neuronal Na/K-ATPase Dysfunction
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批准号:10646335
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项目类别:
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资助金额:$40.0万
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财政年份:2022
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负责人:Alfred L. George
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依托单位:
Administrative Core
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批准号:10657773
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项目类别:
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资助金额:$41.19万
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财政年份:2021
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负责人:Alfred L. George
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Kinetic Imaging Plate Reader for Drug Discovery and Biology
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批准号:10177367
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项目类别:
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资助金额:$59.53万
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财政年份:2021
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负责人:Alfred L. George
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依托单位:
Administrative Core
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批准号:10285156
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项目类别:
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资助金额:$40.77万
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财政年份:2021
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负责人:Alfred L. George
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依托单位:
Decrypting Variants of Uncertain Significance in Long-QT Syndrome
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批准号:10004933
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项目类别:
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资助金额:$4.42万
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财政年份:2020
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负责人:Alfred L. George
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依托单位:
2019 Cardiac Arrhythmia Mechanisms GRC/GRS
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批准号:9755670
-
项目类别:
-
资助金额:$0.5万
-
财政年份:2019
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负责人:Alfred L. George
-
依托单位:
Pilot and Feasibility Component
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批准号:10203941
-
项目类别:
-
资助金额:$8.64万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Channelopathy-Associated Epilepsy Research Center
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批准号:10477447
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项目类别:
-
资助金额:$232.53万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Admin Core
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批准号:10477448
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项目类别:
-
资助金额:$7.3万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Project 1 - High-throughput functional evaluation of ion channel variants in epilepsy
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批准号:10477452
-
项目类别:
-
资助金额:$75.42万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Channelopathy-Associated Epilepsy Research Center
-
批准号:10455341
-
项目类别:
-
资助金额:$2.45万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Channelopathy-Associated Epilepsy Research Center
-
批准号:10247551
-
项目类别:
-
资助金额:$233.99万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Project 1 - High-throughput functional evaluation of ion channel variants in epilepsy
-
批准号:10247556
-
项目类别:
-
资助金额:$75.63万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Kidney Therapeutics: Translating Discoveries into Prevention, Treatment and Cures for Kidney Diseases
-
批准号:10460929
-
项目类别:
-
资助金额:$112.0万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Admin Core
-
批准号:10247552
-
项目类别:
-
资助金额:$7.3万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Channelopathy-Associated Epilepsy Research Center
-
批准号:9792292
-
项目类别:
-
资助金额:$237.2万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Kidney Therapeutics: Translating Discoveries into Prevention, Treatment and Cures for Kidney Diseases
-
批准号:9753225
-
项目类别:
-
资助金额:$115.57万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
Kidney Therapeutics: Translating Discoveries into Prevention, Treatment and Cures for Kidney Diseases
-
批准号:10203936
-
项目类别:
-
资助金额:$113.39万
-
财政年份:2018
-
负责人:Alfred L. George
-
依托单位:
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