Genome-wide association studies (GWAS) provide an unbiased first look at genetic loci involved in aging and noise-induced sensorineural hearing loss and tinnitus. The hearing phenotype, whether audiogram-based or self-report, is regressed against genotyped information at representative single nucleotide polymorphisms (SNPs) across the genome. Findings include the fact that both hearing loss and tinnitus are polygenic disorders, with up to thousands of genes, each of effect size of < 0.02. Smaller human GWAS’ were able to use objective measures and identified a few loci; however, hundreds of thousands of participants have been required for the statistical power to identify significant variants, and GWAS is unable to assess rare variants with mean allele frequency < 1%. Animal studies are required as well because of inability to access the human cochlea. Mouse GWAS builds on linkage techniques and the known phenotypic differences in auditory function between inbred strains. With the advantage that the laboratory environment can be controlled for noise and aging, the Hybrid Mouse Diversity Panel (HDMP) combines 100 strains sequenced at high resolution. Lift-over regions between mice and humans have identified over 17,000 homologous genes. Since most significant SNPs are either intergenic or in introns, and binding sites between species are poorly preserved between species, expression quantitative trait locus information is required to bring humans and mice into agreement. Transcriptome-wide analysis studies (TWAS) can prioritize putative causal genes and tissues. Diverse species, each making a distinct contribution, carry a synergistic advantage in the quest for treatment and ultimate cure of sensorineural hearing difficulties.

全基因组关联研究 (GWAS) 对与衰老和噪声引起的感音神经性听力损失和耳鸣有关的基因位点提供了公正的初步观察。听力表型，无论是基于听力图的还是自我报告的，都会根据整个基因组中代表性单核苷酸多态性 (SNP) 的基因分型信息进行回归。研究结果表明，听力损失和耳鸣都是多基因疾病，有多达数千个基因，每个基因的效应大小均< 0.02。较小的人类 GWAS 能够使用客观测量并确定一些位点；然而，需要数十万参与者的统计能力来识别显着变异，并且 GWAS 无法评估平均等位基因频率 < 1% 的罕见变异。由于无法接触人类耳蜗，因此还需要进行动物研究。小鼠 GWAS 建立在连锁技术和近交系之间听觉功能的已知表型差异的基础上。混合小鼠多样性面板 (HDMP) 的优点是可以控制实验室环境的噪音和老化，结合了 100 个以高分辨率测序的品系。小鼠和人类之间的转移区域已鉴定出超过 17,000 个同源基因。由于最重要的 SNP 要么是基因间的，要么是内含子中的，并且物种之间的结合位点在物种之间保存得很差，因此需要表达数量性状基因座信息来使人类和小鼠达成一致。全转录组分析研究 (TWAS) 可以优先考虑假定的因果基因和组织。不同的物种各自做出了独特的贡献，在寻求治疗和最终治愈感音神经性听力困难的过程中具有协同优势。