Single nucleotide and copy number variants associated with Parkinson disease
Single nucleotide and copy number variants associated with Parkinson disease
批准号:
10409630
负责人:
JAMES ASHE
金额:
$0.0万
依托单位国家:
美国
项目类别:
财政年份:
2019
资助国家:
美国
项目状态:
已结题
起止时间:
2019-04-01 至 2022-09-30
关键词:
AddressAffectAfrican AmericanAreaBiologicalBiological MarkersBiologyBlood TestsCholesterolClinicClinicalClinical TrialsCollectionCommunitiesComputer softwareCopy Number PolymorphismCraniocerebral TraumaDNADNA copy numberDataData SetDiseaseDisease ProgressionEnvironmentEnvironmental Risk FactorEuropeanExposure toFutureGene ExpressionGeneral PopulationGenesGeneticGenetic RiskGenomeGenotypeGoalsHematological DiseaseHeritabilityHispanic AmericansHispanicsIndividualIntakeIntervention TrialJavaLearningLipidsMeasuresMediatingMendelian randomizationMeta-AnalysisMitochondriaMitochondrial DNAMolecularMorbidity - disease rateMutationNatural SelectionsNeurodegenerative DisordersNoiseNuclearNucleic Acid Regulatory SequencesNucleotidesParkinson DiseaseParticipantPathologyPatient CarePatientsPesticidesPharmaceutical PreparationsPopulationPopulation StudyQuantitative Trait LociQuestionnairesResearch PersonnelResourcesRestRiskRunningSample SizeSecondary toSeriesSignal TransductionSingle Nucleotide PolymorphismSusceptibility GeneTest ResultTestingTranscriptTraumatic Brain InjuryUnited States Department of Veterans AffairsVariantVeteransbaseclinical caredisorder riskdrug developmentexperimental studygene environment interactiongene interactiongenetic linkage analysisgenetic risk factorgenetic testinggenetic variantgenome wide association studygenome-wideimprovedinstrumentinterestmRNA Expressionmitochondrial dysfunctionmortalitynew therapeutic targetnovelnovel strategiespesticide exposureprogramsrandomized trialresponserisk stratificationrisk varianttherapeutic targettrait
中文摘要
百万退伍军人计划(MVP)数据集将用于识别新的遗传风险变异
英文摘要
The Million Veteran Program (MVP) data set will be used to identify new genetic risk variants—
including copy number variants (CNVs: deletions and duplications in the genome)—for
Parkinson disease (PD). Previously identified genetic risk factors will be better characterized by
testing all pairwise gene-by-gene interactions and testing if variants associated with mRNA
expression levels are predictive of PD risk using PrediXcan. The MVP intake questionnaire
captured previously identified environmental risk factors such as head trauma (traumatic brain
injury) and pesticide exposure; these will be accounted for in the study through gene-by-
environment tests to determine if the effects of variants are mediated by these exposures. This
will also be the first GWAS of PD to analyse significant Hispanic and African American
populations, which will reveal if the variants identified using individuals of European descent are
generalizable to other populations. In addition, replication of an association between lower
mitochondrial DNA copy number (mtDNA CN) in the blood and PD will be attempted, possibly
establishing mtDNA CN as a biomarker for PD risk and progression, which could later be used
in clinical trials or even in the clinic. mtDNA CN will be measured using a novel approach that
we developed to determine the relative signal intensity for mitochondrial probes on a GWAS
array compared to the corresponding signal intensity for nuclear probes. Mendelian
randomization experiments would then be employed to see if there is evidence that low mtDNA
CN causes PD or whether the PD pathology causes the mtDNA CN to decrease. These
experiments will reveal new information regarding the biology of Parkinson disease, allow for
better risk stratification, and potentially reveal targets for novel therapeutics.
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会议论文
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批准号:8838213
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项目类别:
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资助金额:$0.0万
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财政年份:2012
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负责人:JAMES ASHE
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依托单位:
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批准号:8548964
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资助金额:$0.0万
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财政年份:2012
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批准号:8280117
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资助金额:$0.0万
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财政年份:2012
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负责人:JAMES ASHE
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依托单位:
MOTOR LEARNING RECOGNITION MEMORY IN FRONTAL CORTEX
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批准号:7721377
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资助金额:$1.78万
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依托单位:
Neurophysiology of time production
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批准号:7221262
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资助金额:$3.03万
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财政年份:2006
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依托单位:
Neurophysiology of time production
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批准号:7380054
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资助金额:$3.03万
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财政年份:2006
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Neurophysiology of time production
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批准号:7070873
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资助金额:$3.94万
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财政年份:2006
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负责人:JAMES ASHE
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CEREBELLUM ACTIVATION ASSOCIATED W/ PERFORMANCE CHANGE BUT NOT MOTOR LEARNING
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批准号:6978278
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项目类别:
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资助金额:$3.12万
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财政年份:2004
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负责人:JAMES ASHE
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Cortical control of sequential motor behavior
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批准号:6619863
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资助金额:$21.86万
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财政年份:2001
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Cortical control of sequential motor behavior
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项目类别:
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资助金额:$21.85万
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财政年份:2001
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依托单位:
Cortical control of sequential motor behavior
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批准号:6529961
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资助金额:$21.86万
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依托单位:
Cortical control of sequential motor behavior
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资助金额:$21.85万
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Cortical control of sequential motor behavior
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资助金额:$20.91万
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财政年份:2001
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LEARNING IN THE HUMAN MOTOR CORTEX
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Learning in the human motor cortex
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资助金额:$30.32万
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财政年份:2000
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资助金额:$30.32万
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财政年份:2000
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负责人:JAMES ASHE
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依托单位:
LEARNING IN THE HUMAN MOTOR CORTEX
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资助金额:$26.21万
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财政年份:2000
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Learning in the human motor cortex
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资助金额:$30.32万
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依托单位:
海外基金