Genome-wide Study of Hearing Impairment

听力障碍的全基因组研究

• 批准号: 8567385
• 负责人: Thomas Hoffmann
• 金额: $ 21.02万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-07-01 至 2018-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8567385
• 关键词: Adult; Affect; African American; Age; Aged, 80 and over; Aging; Architecture; Asians; Audiology; Behavior; Biological; Biological Assay; California; Cardiovascular Diseases; Child; Code; Communication; Complex; Data; Development; Diabetes Mellitus; Disease; Early Diagnosis; Elderly; Electronic Health Record; Electronics; Environment; Environmental Risk Factor; Ethnic group; Female; Future; Gender; Genes; Genetic; Genome; Genotype; Health; Health Surveys; Hearing; Hearing problem; Heritability; ICD-9; Impairment; Individual; K-Series Research Career Programs; Latino; Lead; Measures; Medical Records; Paper; Parents; Participant; Pathway interactions; Phenotype; Physical activity; Play; Presbycusis; Public Health; Quality of life; Research; Resources; Retrieval; Risk; Risk Factors; Role; Running; Sample Size; Second Degree Relative; Sensorineural Hearing Loss; Sensory; Single Nucleotide Polymorphism; Smoking; Speech; Surveys; Testing; Tinnitus; Variant; Work; age related; base; cohort; exome sequencing; genetic analysis; genetic epidemiology; genome wide association study; genome-wide; hearing impairment; high risk; improved; innovation; male; member; programs; public health relevance; racial and ethnic; socioeconomics; therapy development

DESCRIPTION (provided by applicant): More than 25% of individuals over age 65 and 50% of individuals over age 80 suffer from varying levels of age- related hearing impairment (AHRI), and adults are losing hearing at earlier ages than in the past. Age-related hearing impairment can make it difficult to communicate and understand speech, and can lead to an overall lower quality of life. Thus it is an important public health concern. There is strong evidence that both genetic and environmental factors play a role in age-related hearing impairment. Although there have been some studies on the genetics of age-related hearing disorders, they have been on limited sample sizes and have not fully explained the heritability of the disease. A previous genome-wide association study of 1,692 individuals implicated one gene, and study of hearing thresholds on 3,417 individuals provided several candidates for further observation. Here we propose a genome-wide association study that is orders of magnitude larger than previous studies in a cohort of 100,000 individuals nested in the Kaiser Research Program on Genes, Environment, and Health. These individuals have a mean age of 63, and already have genome-wide data at over 650,000 single nucleotide polymorphisms (SNPs). We expect that with such a large cohort, we will have much more power to detect loci that affect age-related hearing loss, that may lead to discoveries of additional genes that affect hearing loss. This project provides an efficient and innovative opportunity to obtain a comprehensive understanding of how these genetic factors impact AHRI, which may help identify individuals at greater risk so they can take more preventative measures. Understanding the genetic factors will also lead to better understanding of the underlying biological mechanisms of AHRI, which may improve potential treatments.

描述（由申请人提供）：超过 25% 的 65 岁以上人士和 50% 的 80 岁以上人士患有不同程度的年龄相关性听力障碍 (AHRI)，并且成年人丧失听力的年龄比过去更早。与年龄相关的听力障碍会使沟通和理解言语变得困难，并可能导致整体生活质量下降。因此，它是一个重要的公共卫生问题。有强有力的证据表明，遗传和环境因素在与年龄相关的听力障碍中发挥着作用。尽管已经有一些关于与年龄相关的听力障碍的遗传学研究，但它们的样本量有限，并且没有完全解释该疾病的遗传性。之前一项针对 1,692 人的全基因组关联研究发现了一个基因，而对 3,417 人的听力阈值的研究则提供了几个可供进一步观察的候选基因。在这里，我们提出了一项全基因组关联研究，该研究比之前在凯撒基因、环境和健康研究计划中对 100,000 名个体进行的研究大了几个数量级。这些人的平均年龄为 63 岁，并且已经拥有超过 650,000 个单核苷酸多态性 (SNP) 的全基因组数据。我们预计，有了如此大的队列，我们​​将有更多的能力来检测影响与年龄相关的听力损失的基因座，这可能会导致发现影响听力损失的其他基因。该项目提供了一个有效和创新的机会，以全面了解这些遗传因素如何影响 AHRI，这可能有助于识别风险更大的个体，以便他们采取更多的预防措施。了解遗传因素还将有助于更好地了解 AHRI 的潜在生物学机制，这可能会改善潜在的治疗方法。