Genome-wide Study of Hearing Impairment

描述(申请人提供)：超过25%的65岁以上的人和50%的80岁以上的人患有不同程度的年龄相关性听力障碍(AHRI)，成年人失去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语言变得困难，并可能导致整体生活质量下降。因此，这是一个重要的公共卫生问题。有强有力的证据表明，遗传和环境因素在年龄相关性听力障碍中都起到了作用。虽然已经有一些关于年龄相关性听力障碍的遗传学研究，但他们的样本量有限，并没有完全解释这种疾病的遗传性。此前对1,692名个体进行的全基因组关联研究涉及一种基因，对3,417名个体的听力阈值研究为进一步观察提供了几个候选对象。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嵌套的10万人队列中的研究大几个数量级。这些个体的平均年龄为63岁，并且已经拥有超过650,000个单核苷酸多态(SNPs)的全基因组数据。我们预计，有了这么大的队列，我们将有更多的能力来检测影响年龄相关性听力损失的基因，这可能会导致发现更多影响听力损失的基因。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高的个人，以便他们能够采取更多预防措施。了解遗传因素也将有助于更好地了解AHRI的潜在生物学机制，这可能会改进潜在的治疗方法。

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.