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一项全基因组关联研究揭示了自我报告听力正常的个体在噪声缺陷中的言语多基因结构

A genome-wide association study reveals a polygenic architecture of speech-in-noise deficits in individuals with self-reported normal hearing

Nature 等信源发布 2024-06-07 18:33

可切换为仅中文


AbstractSpeech-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.

摘要噪声中的言语(SIN)感知是听力损失患者的主要抱怨。SIN表现差异很大,即使在听力正常的个体中也是如此。目前的全基因组关联研究(GWAS)调查了在安静情况下自我报告听力正常的个体SIN缺陷的遗传基础。

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对来自UB Biobank队列的279911人进行了研究,尽管有58847人报告安静时听力正常,但仍有SIN缺陷。GWAS鉴定了996个单核苷酸多态性(SNP),在四个基因组位点上实现了显着性(p<5*10-8)。跨越21个基因座的720个SNP具有提示意义(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.

GWAS信号富含脑组织,例如前扣带回皮层,背外侧前额叶皮层,内嗅皮层,额叶皮层,海马和颞下皮层。耳蜗细胞类型与SIN缺陷无显着相关性。SIN缺陷与各种健康特征有关,包括神经精神,感觉,认知,代谢,心血管和炎症状况。

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.

对242名健康年轻人进行了复制分析。复制分析使用了自我报告的语音感知,听力阈值(0.25–16 kHz)和失真产物耳声发射(1–16 kHz)。通过自我报告的言语感知测量复制了73个SNP。

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..

211个SNP被至少一个复制,66个被至少两个听力学测量复制。所有听力学测量均复制了MAPT,GRM3和HLA-DQA1附近或内部的12个SNP。本研究强调了自我报告听力正常的个体中SIN缺陷的多基因结构。。

IntroductionFrom ordering beverages in a noisy café to maintaining conversation at a cocktail party, we process speech-in-noise (SIN) to be efficient at routine tasks. SIN processing is challenging for individuals with audiometric hearing loss (e.g.,1). Notably, about 10–15% of individuals report SIN deficits despite normal audiograms2,3.

简介从在嘈杂的咖啡馆点饮料到在鸡尾酒会上保持对话,我们处理噪音中的言语(SIN)以提高日常工作的效率。对于听力损失的个体(例如1),SIN处理具有挑战性。值得注意的是,尽管听力正常,但约有10-15%的人报告SIN缺陷2,3。

Around 10% of patients seeking professional help for communication problems exhibit clinically normal audiograms4,5,6. SIN deficits are associated with an increased risk of dementia, Alzheimer's disease (AD), depressive symptoms, and impaired cognitive functioning7,8. Emerging evidence suggests that SIN deficits could be a valuable preclinical indicator of AD-related dementia9.SIN processing requires a dynamic interaction between auditory and cognitive systems involving a series of interdependent biological processes (e.g.,10).

大约10%的寻求沟通问题专业帮助的患者表现出临床上正常的听力图4,5,6。SIN缺陷与痴呆,阿尔茨海默病(AD),抑郁症状和认知功能受损的风险增加有关7,8。新出现的证据表明,SIN缺陷可能是AD相关痴呆的一个有价值的临床前指标9。SIN处理需要听觉和认知系统之间的动态相互作用,涉及一系列相互依赖的生物过程(例如10)。

Sensory cells must process acoustic signals to produce accurate neural codes during SIN processing, helping the higher-order neurons “group” the parts of the signal representing the target and background noise11,12,13. The auditory grouping facilitates unmasking target signals at the cortex14. Cognitive factors, such as working memory, selective attention, and language, play a critical role in SIN processing15,16.

感觉细胞必须处理声音信号,以在SIN处理过程中产生准确的神经代码,帮助高阶神经元“分组”代表目标和背景噪声的信号部分11,12,13。听觉分组有助于揭示皮层的目标信号14。认知因素,如工作记忆,选择性注意和语言,在SIN处理中起着至关重要的作用15,16。

SIN performance varies among individuals with hearing loss and those using hearing aids and cochlear implants17,18. SIN performance varies substantially even in individuals with clinically normal hearing thresholds12. The biological basis of individual differences in SIN perception remains elusive. We hypothesized that genetic variability could explain individual differences in SIN deficits.Suprathreshold spectral and temporal auditory processes required for SIN processing exhibit a polygenic inheritan.

SIN表现因听力损失者和使用助听器和人工耳蜗的人而异17,18。即使在临床听力阈值正常的个体中,SIN的表现也有很大差异12。罪感个体差异的生物学基础仍然难以捉摸。我们假设遗传变异可以解释SIN缺陷的个体差异。SIN处理所需的超阈值光谱和时间听觉过程表现出多基因遗传。

Data availability

数据可用性

The study used the UK Biobank database. The database is publicly available through the UK Biobank website: https://www.ukbiobank.ac.uk/. The data used for the replication analysis will be shared on dbGaP after the completion of the project: R21DC016704-01A1. The data used for cochlear cell type enrichment analysis were obtained from Boussaty et al.

这项研究使用了英国生物库数据库。该数据库可通过英国生物银行网站公开获得:https://www.ukbiobank.ac.uk/.项目完成后,用于复制分析的数据将在dbGaP上共享:R21DC016704-01A1。用于耳蜗细胞类型富集分析的数据来自Boussaty等人。

(2023) from the following: https://umgear.org//index.html?share_id=f526abfe&gene_symbol_exact_match=1. GWAS summary statistics can be found at: https://my.locuszoom.org/gwas/752608/?token=3b4cea1d3178406eaaf2ea2e92429332..

(2023)来自以下内容:https://umgear.org//index.html?share_id=f526abfe&gene_symbol_exact_match=1.GWAS摘要统计信息可在以下网址找到:https://my.locuszoom.org/gwas/752608/?token=3b4cea1d3178406eaaf2ea2e92429332..

AbbreviationsGWAS:

缩写GWAS:

Genome-wide association study

全基因组关联研究

SNP:

单核苷酸多态性:

Single nucleotide polymorphism

单核苷酸多态性

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Download referencesAcknowledgementsThe study was funded by the National Institute on Deafness and Other Communication Disorders Grant R21DC016704-01A1.Author informationAuthors and AffiliationsDepartment of Communication Sciences and Disorders, University of Iowa, 250 Hawkins Dr, Iowa City, IA, 52242, USAIshan Sunilkumar Bhatt, Juan Antonio Raygoza Garay, Srividya Grama Bhagavan & Valerie IngallsHolden Comprehensive Cancer Center, University of Iowa, Iowa City, IA, 52242, USAJuan Antonio Raygoza GarayDepartment of Microbiology and Cell Science, University of Florida, Gainesville, FL, 32608, USARaquel DiasDepartment of Integrative Structural and Computational Biology, Scripps Research Institute, La Jolla, CA, 92037, USAAli TorkamaniAuthorsIshan Sunilkumar BhattView author publicationsYou can also search for this author in.

下载参考文献致谢该研究由国家耳聋和其他沟通障碍研究所资助R21DC016704-01A1。作者信息作者和附属机构爱荷华大学沟通科学与障碍系,250霍金斯博士,爱荷华州爱荷华市,52242,USAIshan Sunilkumar Bhatt,Juan Antonio Raygoza Garay,Srividya Grama Bhagavan&Valerie IngallsHolden综合癌症中心,爱荷华州爱荷华州爱荷华市,52242,USAHANO Raygoza Garay佛罗里达大学微生物学和细胞科学系,佛罗里达州盖恩斯维尔,佛罗里达州,32608,USARaquel DiasDepartment of Integrative Structural and Computational Biology,Scripps Research Institute,La Jolla,CA,92037,USAAli TorkamaniAuthorsIshan Sunilkumar BhattView Author Publications您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsI.S.B. conducted the analysis, prepared figures, tables, and wrote the initial manuscript draft. J.A.R.G. wrote the codes for conducting genomic quality control. S.G.B. and V.I. prepared frequency table, R.D. helped with conducting the analysis, and A.T.

PubMed谷歌学术贡献。S、 B.进行分析,准备数字,表格,并撰写初稿。J、 A.R.G.编写了进行基因组质量控制的代码。S、 G.B.和V.I.准备了频率表,R.D.帮助进行了分析,A.T。

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Reprints and permissionsAbout this articleCite this articleBhatt, I.S., Garay, J.A.R., Bhagavan, S.G. et al. A genome-wide association study reveals a polygenic architecture of speech-in-noise deficits in individuals with self-reported normal hearing.

转载和许可本文引用本文Bhatt,I.S.,Garay,J.A.R.,Bhagavan,S.G.等人。一项全基因组关联研究揭示了自我报告听力正常的个体在噪声缺陷中言语的多基因结构。

Sci Rep 14, 13089 (2024). https://doi.org/10.1038/s41598-024-63972-2Download citationReceived: 14 November 2023Accepted: 04 June 2024Published: 07 June 2024DOI: https://doi.org/10.1038/s41598-024-63972-2Share this articleAnyone you share the following link with will be able to read this content:Get shareable linkSorry, a shareable link is not currently available for this article.Copy to clipboard.

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KeywordsSpeech-in-noise deficitsHidden hearing lossAge-related hearing difficulty in noiseSelf-reported speech perceptionAudiogramHearing thresholdsDistortion-product otoacoustic emissionsExtended-high frequencyGenome-wide associationMicrotubule-associated protein tauGlutamate metabotropic receptor 3Glutamate metabotropic receptor 7.

关键词言语缺陷与听力损失相关的听力障碍自我报告的言语感知听力图听力阈值畸变产物耳声发射倾向于高频全基因组关联微管相关蛋白tau谷氨酸代谢型受体3谷氨酸代谢型受体7。

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