Genomic Variability and Symptomatology After Traumatic Brain Injury
脑外伤后的基因组变异和症状学
基本信息
- 批准号:8257193
- 负责人:
- 金额:$ 42.2万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-27 至 2014-07-31
- 项目状态:已结题
- 来源:
- 关键词:AccountingAmericanAwardAwarenessBehaviorBehavioralBiologicalBiological MarkersCaringChronic DiseaseCicatrixClassificationClinical SciencesCognitionCognitiveCoupledDNADataDatabasesDemographic FactorsDevelopmentEmotionalEmotionsEpidemicEvidence based interventionFamilyFamily dynamicsFemaleGenderGenesGeneticGenomicsGenotypeGoalsGonadal HormonesImpairmentIncidenceIndividualInjuryInstitutesInterdisciplinary StudyInvestigationLeftMitochondriaNervous System TraumaNuclearOxidative PhosphorylationPathway interactionsPatientsPhenotypePlayPopulationPredispositionProductionQuality of lifeResearchResourcesRiskRisk AssessmentRoleSamplingSeveritiesSurvivorsSymptomsTimeTranslatingTranslational ResearchTrauma ResearchTraumatic Brain InjuryWorkbaseclinical applicationdaily functioningexperiencegenetic associationmitochondrial genome
项目摘要
DESCRIPTION (provided by applicant): Traumatic Brain Injury (TBI) is frequently referred to as a "silent epidemic" because its lasting impairments do not leave visible scars and public awareness has historically been limited. In reality, a TBI marks the beginning of a chronic disease, from which 5.3 million Americans currently suffer persistent symptoms that cause major limitations in daily function and significantly impact quality of life for decades after the injury. Regardless of severity of injury, 76% of TBI survivors have at least one symptom and 53% have at least 3 symptoms at one year post injury. The symptoms seen most frequently post-TBI, and on which this application focuses, are those that influence cognition, behavior, and emotion. These symptoms have a significant impact on employability, quality of life, and family dynamics. It is completely unknown why some patients fully recover and are symptom free, while others who have the same extent of injury, same care, and same demographic factors develop lifelong symptoms. The long-term goal of our research is to identify the biological underpinnings influencing variability in symptomatology post- TBI and to use this information to develop evidence-based interventions that are tailored to an individual's genomic risk profile. Our overall objective of this application is to determine the extent that variability in genes involved in the mitochondrial oxidative phosphorylation (OXPHOS) pathway, responsible for cellular energy production, is responsible for variability in symptoms related to cognition, behavior, and emotion post-TBI. We are focusing on the OXPHOS pathway because availability of cellular energy impacts extent of neurological damage after TBI and our preliminary data shows genetic variability in the mitochondrial genome and efficiency of the OXPHOS pathway impact symptomatology up to 2 years post-TBI. Our data also indicate a possible moderating gender effect on the influence of mitochondrial genotype on both OXPHOS efficiency and symptomatology after TBI. To date all of our work has been with the mitochondrial genome; however the majority of genes involved in the OXPHOS pathway are nuclear in origin. This project will evaluate the nuclear genes involved in the OXPHOS pathway using a tagging SNP, candidate pathway, genetic association, with predictive analysis approach to look at both nuclear and mitochondrial contributions to cognitive, behavioral, and emotional symptomatology post-TBI. This application proposes a logical next step in our line of investigation that is necessary in order to fully understand the impact that genetic variability in the OXPHOS pathway has on symptom variability observed in patients after TBI, progress toward risk prediction that includes objective genetic data, and eventually translate these findings to reduce the incidence and severity of symptoms experienced by survivors of TBI.
PUBLIC HEALTH RELEVANCE: Traumatic Brain Injury (TBI) is frequently referred to as a "silent epidemic" because its lasting impairments do not leave visible scars and public awareness has historically been limited. In reality, a TBI marks the beginning of a chronic disease, from which 5.3 million Americans currently suffer persistent symptoms that cause major limitations in daily function and significantly impact quality of life for decades after the injury. It is completely unknown why some patients fully recover and are symptom free, while others who have the same extent of injury, same care, and same demographic factors develop lifelong symptoms. The goal of this application is to investigate the role that genetic variability plays in susceptibility to symptoms after TBI with the hope of eventually translating this information into risk assessment and tailored therapies for TBI survivors to reduce the incidence and severity of symptoms post-TBI.
描述(申请人提供):创伤性脑损伤(TBI)通常被称为“无声流行病”,因为它的持久损伤不会留下明显的伤疤,而且公众意识历来有限。事实上,脑外伤标志着一种慢性病的开始,目前有530万美国人患有持续的症状,这些症状导致日常功能严重受限,并在受伤后几十年内显著影响生活质量。无论损伤的严重程度如何,76%的创伤幸存者在受伤后一年内至少有一种症状,53%的人至少有三种症状。颅脑损伤后最常见的症状,也是本应用程序关注的重点,是那些影响认知、行为和情绪的症状。这些症状对就业能力、生活质量和家庭动力有重大影响。完全不知道为什么一些患者完全康复并没有症状,而另一些具有相同程度的伤害、相同的护理和相同的人口统计因素的患者会出现终生症状。我们研究的长期目标是确定影响脑外伤后症状学变异性的生物学基础,并利用这些信息开发针对个体基因组风险概况而量身定做的循证干预措施。我们这项应用的总体目标是确定参与线粒体氧化磷酸化(OXPHOS)途径的基因的可变性在多大程度上负责细胞能量的产生,从而导致脑损伤后与认知、行为和情绪相关的症状的可变性。我们将重点放在OXPHOS途径上,因为细胞能量的可获得性会影响脑损伤后神经损害的程度,我们的初步数据显示,线粒体基因组中的遗传变异和OXPHOS途径的效率会影响脑损伤后长达2年的症状。我们的数据还表明,在脑外伤后线粒体基因对OXPHOS效率和症状的影响中,性别效应可能起到调节作用。到目前为止,我们所有的工作都是关于线粒体基因组的;然而,参与OXPHOS途径的大多数基因都是起源于核的。该项目将使用标记SNP、候选路径、遗传关联和预测性分析方法来评估OXPHOS途径中涉及的核基因,以查看核和线粒体对脑损伤后认知、行为和情绪症状的贡献。这一应用为我们的研究提出了一个合乎逻辑的下一步,这是必要的,以便充分了解OXPHOS途径中的遗传变异对脑损伤后患者观察到的症状可变性的影响,朝着包括客观遗传数据的风险预测迈进,并最终将这些发现转化为减少脑损伤幸存者所经历的症状的发生率和严重程度。
与公共卫生相关:创伤性脑损伤(TBI)经常被称为“无声流行病”,因为它的持久损伤不会留下明显的伤疤,而且公众的意识历来有限。事实上,脑外伤标志着一种慢性病的开始,目前有530万美国人患有持续的症状,这些症状导致日常功能严重受限,并在受伤后几十年内显著影响生活质量。完全不知道为什么一些患者完全康复并没有症状,而另一些具有相同程度的伤害、相同的护理和相同的人口统计因素的患者会出现终生症状。该应用程序的目标是研究遗传变异在脑外伤后症状易感性中的作用,希望最终将这些信息转化为脑外伤幸存者的风险评估和量身定制的治疗,以降低脑外伤后症状的发生率和严重程度。
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)
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Yvette P Conley其他文献
Stress and Coping in Patients With Cancer With Depression and Sleep Disturbance.
患有抑郁症和睡眠障碍的癌症患者的压力和应对方法。
- DOI:
10.1188/24.onf.243-262 - 发表时间:
2024 - 期刊:
- 影响因子:1.9
- 作者:
Alejandra Calvo;Joosun Shin;C. Harris;L. Morse;Steven Paul;Bruce Cooper;Yvette P Conley;F. Wright;M. Hammer;J. Levine;C. Miaskowski - 通讯作者:
C. Miaskowski
Psychoneurological symptom cluster trajectories in individuals treated for early-stage breast cancer
接受早期乳腺癌治疗的个体的心理神经症状群轨迹
- DOI:
- 发表时间:
2023 - 期刊:
- 影响因子:3.1
- 作者:
Susan C. Grayson;Susan M Sereika;Yvette P Conley;Catherine M. Bender;Katrina Carr;Susan Wesmiller - 通讯作者:
Susan Wesmiller
Self-Reported Cancer-Related Cognitive Impairment in Patients With Breast Cancer Is Associated With Potassium Channel Gene Polymorphisms.
乳腺癌患者自我报告的癌症相关认知障碍与钾通道基因多态性相关。
- DOI:
- 发表时间:
2024 - 期刊:
- 影响因子:1.9
- 作者:
K. Oppegaard;M. Hammer;Yvette P Conley;C. Harris;Bruce Cooper;Steven Paul;Joosun Shin;L. Morse;G. M. Abrams;J. Levine;C. Miaskowski - 通讯作者:
C. Miaskowski
Yvette P Conley的其他文献
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{{ truncateString('Yvette P Conley', 18)}}的其他基金
Epigenomics of Patient Outcomes after Traumatic Brain Injury
脑外伤后患者预后的表观基因组学
- 批准号:
8769489 - 财政年份:2014
- 资助金额:
$ 42.2万 - 项目类别:
Epigenomics of Patient Outcomes after Aneurysmal SAH
动脉瘤性蛛网膜下腔出血后患者预后的表观基因组学
- 批准号:
8677625 - 财政年份:2012
- 资助金额:
$ 42.2万 - 项目类别:
Epigenomics of Patient Outcomes after Aneurysmal SAH
动脉瘤性蛛网膜下腔出血后患者预后的表观基因组学
- 批准号:
9099553 - 财政年份:2012
- 资助金额:
$ 42.2万 - 项目类别:
Epigenomics of Patient Outcomes after Aneurysmal SAH
动脉瘤性蛛网膜下腔出血后患者预后的表观基因组学
- 批准号:
8856367 - 财政年份:2012
- 资助金额:
$ 42.2万 - 项目类别:
Epigenomics of Patient Outcomes after Aneurysmal SAH
动脉瘤性蛛网膜下腔出血后患者预后的表观基因组学
- 批准号:
8311979 - 财政年份:2012
- 资助金额:
$ 42.2万 - 项目类别:
Epigenomics of Patient Outcomes after Aneurysmal SAH
动脉瘤性蛛网膜下腔出血后患者预后的表观基因组学
- 批准号:
8548411 - 财政年份:2012
- 资助金额:
$ 42.2万 - 项目类别:
Genomic Variability and Symptomatology After Traumatic Brain Injury
脑外伤后的基因组变异和症状学
- 批准号:
8514736 - 财政年份:2011
- 资助金额:
$ 42.2万 - 项目类别:
Genomic Variability and Symptomatology After Traumatic Brain Injury
脑外伤后的基因组变异和症状学
- 批准号:
8339353 - 财政年份:2011
- 资助金额:
$ 42.2万 - 项目类别:
Targeting Research and Academic Training of Nurses in Genomics
针对基因组学护士的研究和学术培训
- 批准号:
10207064 - 财政年份:2006
- 资助金额:
$ 42.2万 - 项目类别:
Targeted Research and Academic Training of Nurses in Genomics
基因组学护士的针对性研究和学术培训
- 批准号:
8484451 - 财政年份:2006
- 资助金额:
$ 42.2万 - 项目类别:
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