Shared Genetic and Environmental Influences on Age-Related Hearing Loss, Cognitive Decline, and Dementia Risk

遗传和环境对与年龄相关的听力损失、认知能力下降和痴呆风险的共同影响

• 批准号: 10658077
• 负责人: John Blangero
• 金额: $ 77.16万
• 依托单位: BOSTON CHILDREN'S HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-05-15 至 2028-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10658077
• 关键词: 18 year old; Age; Aging; Alzheimer' s disease related dementia; Alzheimer' s disease risk; American; Amyloid beta-42; Animals; Audiology; Auditory Threshold; Biological; Biological Markers; Blood; Blood specimen; Boston; Brain; Case/Control Studies; Cognition; Cognitive; Data; Dementia; Diagnosis; Elderly; Environmental Risk Factor; Ethnic Origin; Family history of; Follow-Up Studies; Future; Genes; Genetic; Genetic Variation; Genetic study; Genomic Segment; Genomics; Genotype; Health; Health Sciences; Hearing; Hearing Tests; Heritability; Human; Image; Impaired cognition; Individual; Lead; Life; Link; Measures; Medical; Mental Health; Mexican Americans; Neurofilament-L; Participant; Pathogenesis; Pathway interactions; Pediatric Hospitals; Pharmaceutical Preparations; Phenotype; Physiological; Population; Presbycusis; Prevalence; Principal Investigator; Quality of life; Random Allocation; Research; Research Personnel; Resources; Role; Sample Size; Sampling; Sensorineural Hearing Loss; Structure; Testing; Texas; Universities; Variant; age related; aging brain; aging population; cochlear synaptopathy; cognitive ability; cognitive skill; cohort; comorbidity; cost effective; dementia risk; design; endophenotype; genetic pedigree; genome wide association study; hearing impairment; improved; indexing; insight; normal hearing; novel; pathological aging; physical conditioning; pleiotropism; tau Proteins; tau-1; trait; whole genome

PROJECT SUMMARY/ABSTRACT Good hearing and cognitive skills are critical to maintaining later-life quality yet decline with advancing age. Hearing thresholds and cognitive abilities are correlated, and a diagnosis of age-related sensorineural hearing loss increases risk for Alzheimer’s disease and related dementias. These findings suggest that shared genetic and environmental factors influence presbycusis, cognitive decline, and dementia risk. We call this the “com- mon pathway” hypothesis. In our previous study of individuals from randomly selected Mexican American pedi- grees, we found genetic correlations between hearing and cognitive abilities, providing support for the common pathway hypothesis. However, the specific common genetic and environmental pathways have yet to be identi- fied. Here, we propose to measure hearing abilities, cognitive abilities, and putative dementia biomarkers (t- tau, p-tau, Aβ42/40, and NF-L) in an additional 600 Mexican American participants, increasing our total sample size to 1,300 and thereby providing sufficient power for further analyses, including identification of specific ge- netic/environmental risk factors. Our specific aims are (1) to quantify age-related and shared genetic influences on hearing, cognition, and dementia biomarkers; (2) to interrogate whole-genome sequence data, medical in- formation, and geospatial data in order to identify specific genetic and environmental influences on these traits; (3) to provide direct evidence of pleiotropy between hearing loss and dementia risk per se; and (4) to validate measures of cochlear synaptopathy, a physiological early warning sign of hearing loss that is undetectable via traditional hearing tests, as phenotypes for future aging studies. Measuring hearing abilities, cognitive abilities, and dementia biomarkers together in the same individuals may dramatically improve the odds of delineating specific factors influencing one or more of these crucial aspects of aging. Such discoveries may in turn provide insights and strategies for increasing the numbers of Americans who successfully age. Drs. Samuel Mathias and David Glahn at Boston Children’s Hospital and Dr. John Blangero at University of Texas Rio Grande Val- ley are co-principal investigators on this application. Dr. Amy Garrett at University of Texas Health Science Center San Antonio will lead a subcontract. Given the wealth of phenotypic, environmental and genetic data already available in this cohort, the proposed study represents a readily available, cost-effective, and powerful resource for elucidating the mechanisms of aging.

项目摘要/摘要 良好的听力和认知能力对于维持后期的质量至关重要，但随着年龄的增长而下降。 听力阈值和认知能力是相关的，并且是与年龄相关的感官听力的诊断 损失增加了阿尔茨海默氏病和相关痴呆症的风险。这些发现表明共享遗传 环境因素会影响长老会，认知能力下降和痴呆症风险。我们将其称为“ com- Mon Pathway”假设。 Grees，我们发现听力与认知能力之间的遗传相关性，为共同的支持提供了支持 途径假设。但是，尚未确定特定的常见遗传和环境途径 - 填充。在这里，我们建议衡量听力能力，认知能力和推定的痴呆生物标志物（t- tau，p-tau，aβ42/40和nf-l）在另外600名墨西哥人参与者中，增加了我们的总样本 大小至1,300，从而提供了足够的功率来进一步分析，包括识别特定的GE- 网络/环境风险因素。我们的具体目的是（1）量化与年龄有关的遗传影响和共享的遗传影响 听力，认知和痴呆症生物标志物； （2）询问全基因组序列数据，医学 形成和地理空间数据是为了确定对这些特征的特定遗传和环境影响； （3）提供听力损失和痴呆症风险之间的多效性的直接证据； （4）验证 人工耳蜗突触病的度量，这是听力损失的物理预警信号，无法通过 传统的听力测试，作为未来衰老研究的表型。衡量听力能力，认知能力， 和痴呆症生物标志物在同一个人中一起可能会大大提高描述的几率 影响衰老的关键方面之一的特定因素。这样的发现可能会提供 增加成功衰老的美国人人数的见解和策略。博士。塞缪尔·马蒂亚斯（Samuel Mathias） 波士顿儿童医院的大卫·格拉恩（David Glahn）和德克萨斯大学里奥格兰德分校的约翰·布兰格罗（John Blangero）博士 - Ley是该应用程序的联合首席调查员。德克萨斯大学健康科学的艾米·加勒特博士 圣安东尼奥中心将领导分包合同。鉴于大量的表型，环境和遗传数据 拟议的研究已经在该队列中可用，代表了一项易于使用的，具有成本效益且功能强大的 阐明衰老机制的资源。