PDF(Pubmed)
Abstract：
Speech-in-noise (SIN) perception is a primary complaint of individuals with audiometric hearing loss. SIN performance varies drastically, even among individuals with normal hearing. The present genome-wide association study (GWAS) investigated the genetic basis of SIN deficits in individuals with self-reported normal hearing in quiet situations. GWAS was performed on 279,911 individuals from the UB Biobank cohort, with 58,847 reporting SIN deficits despite reporting normal hearing in quiet. GWAS identified 996 single nucleotide polymorphisms (SNPs), achieving significance (p < 5*10-8) across four genomic loci. 720 SNPs across 21 loci achieved suggestive significance (p < 10-6). GWAS signals were enriched in brain tissues, such as the anterior cingulate cortex, dorsolateral prefrontal cortex, entorhinal cortex, frontal cortex, hippocampus, and inferior temporal cortex. Cochlear cell types revealed no significant association with SIN deficits. SIN deficits were associated with various health traits, including neuropsychiatric, sensory, cognitive, metabolic, cardiovascular, and inflammatory conditions. A replication analysis was conducted on 242 healthy young adults. Self-reported speech perception, hearing thresholds (0.25-16 kHz), and distortion product otoacoustic emissions (1-16 kHz) were utilized for the replication analysis. 73 SNPs were replicated with a self-reported speech perception measure. 211 SNPs were replicated with at least one and 66 with at least two audiological measures. 12 SNPs near or within MAPT, GRM3, and HLA-DQA1 were replicated for all audiological measures. The present study highlighted a polygenic architecture underlying SIN deficits in individuals with self-reported normal hearing.
摘要：
语音噪声（SIN）感知是听力损失患者的主要主诉。SIN性能差异很大，即使是听力正常的人。当前的全基因组关联研究（GWAS）调查了在安静情况下自我报告正常听力的个体中SIN缺陷的遗传基础。对来自UB生物库队列的279,911名个体进行了GWAS，58,847人报告SIN缺陷，尽管报告安静的听力正常。GWAS鉴定出996个单核苷酸多态性(SNPs)，在四个基因组基因座中实现显著性(p<5*10-8)。跨越21个基因座的720个SNP达到提示意义(p<10-6)。GWAS信号在脑组织中富集，比如前扣带皮质，背外侧前额叶皮质,内嗅皮层,额叶皮质,海马体,和颞下皮质.耳蜗细胞类型与SIN缺陷没有显着关联。SIN缺陷与各种健康特征有关，包括神经精神病学,感官,认知，新陈代谢，心血管,和炎症条件。对242名健康的年轻人进行了复制分析。自我报告的言语感知，听力阈值（0.25-16kHz），和失真产物耳声发射（1-16kHz）用于复制分析。用自我报告的言语感知量度复制了73个SNP。211个SNP用至少一个和66个SNP用至少两个听力学措施进行复制。MAPT附近或内部的12个SNP，GRM3和HLA-DQA1在所有听力学措施中均被复制。本研究强调了自我报告正常听力的个体SIN缺陷的多基因结构。
