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.

项目概要/摘要 良好的听力和认知技能对于维持晚年生活质量至关重要，但会随着年龄的增长而下降。 听力阈值和认知能力是相关的，诊断与年龄相关的感音神经性听力 这些发现表明，共同的遗传基因缺失会增加患阿尔茨海默病和相关痴呆症的风险。 环境因素会影响老年性耳聋、认知能力下降和痴呆风险。 在我们之前对随机选择的墨西哥裔美国儿童的个体进行的研究中。 格里斯，我们发现听力和认知能力之间存在遗传相关性，为常见的观点提供了支持 然而，具体的共同遗传和环境途径尚未确定。 在这里，我们建议测量听力能力、认知能力和假定的痴呆生物标志物（t- tau、p-tau、Aβ42/40 和 NF-L）在另外 600 名墨西哥裔美国人参与者中，增加了我们的样本总数 大小为 1,300，从而为进一步分析提供足够的能力，包括识别特定的基因 我们的具体目标是（1）量化与年龄相关和共同的遗传影响。 关于听力、认知和痴呆生物标志物；(2) 询问全基因组序列数据、医学研究 形成和地理空间数据，以确定对这些性状的特定遗传和环境影响； (3) 提供听力损失和痴呆风险本身之间多效性的直接证据；(4) 进行验证； 耳蜗突触病的测量，这是听力损失的生理早期预警信号，无法通过以下方式检测到 传统的听力测试，作为未来衰老研究的表型，测量听力能力、认知能力、 和痴呆症生物标志物在同一个人身上可能会大大提高描述的可能性 这些发现反过来可能会提供影响衰老的一个或多个关键方面的具体因素。 塞缪尔·马蒂亚斯博士提出了增加成功老龄化美国人数量的见解和策略。 波士顿儿童医院的 David Glahn 和德克萨斯大学里奥格兰德瓦尔分校的 John Blangero 博士 ley 是该应用程序的联合首席研究员，德克萨斯大学健康科学分校的 Amy Garrett 博士。 鉴于丰富的表型、环境和遗传数据，圣安东尼奥中心将领导一份分包合同。 拟议的研究已经在该队列中可用，代表了一种易于获得、具有成本效益且强大的研究 阐明衰老机制的资源。