Noise Exposure and Distortion Product Otoacoustic Emission Suprathreshold Amplitudes: A Genome-Wide Association Study.
Noise Exposure and Distortion Product Otoacoustic Emission Suprathreshold Amplitudes: A Genome-Wide Association Study.
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DOI：
10.1159/000514143
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发表时间：
2021
影响因子：
1.6
通讯作者：
Friedman RA
中科院分区：
文献类型：
--
作者：
Lavinsky J;Kasperbauer G;Bento RF;Mendonça A;Wang J;Crow AL;Allayee H;Friedman RA
尽管已经进行了几项候选基因关联研究来调查人类噪声性听力损失（NIHL），但大多数研究都动力不足，不可复制，并且仅占遗传风险的一小部分。小鼠全基因组关联研究（GWAS）已经彻底改变了遗传学领域，并导致发现了数百个涉及复杂性状的基因。杂交小鼠多样性小组（HMDP）是一个经典的近交系和重组近交系的集合，其基因组已经以高分辨率进行基因分型或测序。为了进一步研究NIHL的遗传学，我们报告了第一个基于畸变产物耳声发射（DPOAE）测量和HMDP的GWAS。共102株（n = 635）的HMDP进行了评价的基础上DPOAE阈上振幅噪声暴露前后。DPOAE振幅变化分别设置为每个频率（8、11.3、16、22.6和32 kHz）的主要音调的60 dB和70 dB SPL。这些值提供了外毛细胞完整性的间接评估。将6周龄的小鼠暴露于108 dB SPL的10 kHz倍频程噪声中2小时。为了进行局部表达数量性状基因座（eQTL）分析，使用来自64个杂交小鼠品系的耳蜗RNA生成基因表达微阵列谱（n = 3个阵列/品系）。几个新的位点被确定，并优先考虑与NIHL相关的位置候选基因，特别是在噪声暴露后（基线时1个位点，暴露后5个位点）。在这6个基因座中，共35个候选基因被鉴定出至少1个探针，其表达在耳蜗中受显著的顺式eQTL调控。在仔细分析基于耳蜗基因表达的候选基因后，优先考虑2个候选基因：Eya 1（基线）和Efr 3a（暴露后）。第一次，关联分析与人口结构的校正被用来映射几个位点的听力性状的近交系小鼠的基础上，噪声暴露前后的DPOAE阈上振幅。我们的研究结果确定了一些新的位点和候选基因的易感性NIHL，特别是Eya 1和Efr 3a基因。我们的研究结果验证了HMDP检测NIHL易感基因的能力。
Although several candidate-gene association studies have been conducted to investigate noise-induced hearing loss (NIHL) in humans, most are underpowered, unreplicated and account for only a fraction of the genetic risk. Mouse genome-wide association studies (GWASs) have revolutionized the field of genetics and have led to the discovery of hundreds of genes involved in complex traits. The Hybrid Mouse Diversity Panel (HMDP) is a collection of classic inbred and recombinant inbred strains whose genomes have been either genotyped at high resolution or sequenced. To further investigate the genetics of NIHL, we report the first GWAS based on distortion product otoacoustic emission (DPOAE) measurements and the HMDP. A total of 102 strains (n = 635) from the HMDP were evaluated based on DPOAE suprathreshold amplitudes before and after noise exposure. DPOAE amplitude variation was set at 60 dB and 70 dB SPL of the primary tones for each frequency separately (8, 11.3, 16, 22.6, and 32 kHz). These values provided an indirect assessment of outer hair cell integrity. Six-week-old mice were exposed for 2 hours to 10 kHz octave-band noise at 108 dB SPL. To perform local expression quantitative trait locus (eQTL) analysis, gene expression microarray profiles were generated using cochlear RNA from 64 hybrid mouse strains (n = 3 arrays per strain). Several new loci were identified and positional candidate genes associated with NIHL were prioritized, especially after noise exposure (1 locus at baseline and 5 loci after exposure). A total of 35 candidate genes in these 6 loci were identified with at least 1 probe whose expression was regulated by a significant cis-eQTL in the cochlea. After careful analysis of the candidate genes based on cochlear gene expression, 2 candidate genes were prioritized: Eya1 (baseline) and Efr3a (post-exposure). For the first time, an association analysis with correction for population structure was used to map several loci for hearing traits in inbred strains of mice based on DPOAE suprathreshold amplitudes before and after noise exposure. Our results identified a number of novel loci and candidate genes for susceptibility to NIHL, especially the Eya1 and Efr3a genes. Our findings validate the power of the HMDP for detecting NIHL susceptibility genes.
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影响因子：
4.5
作者：
Farber CR;Bennett BJ;Orozco L;Zou W;Lira A;Kostem E;Kang HM;Furlotte N;Berberyan A;Ghazalpour A;Suwanwela J;Drake TA;Eskin E;Wang QT;Teitelbaum SL;Lusis AJ
通讯作者：
Lusis AJ
影响因子：
--
作者：
Park CC;Gale GD;de Jong S;Ghazalpour A;Bennett BJ;Farber CR;Langfelder P;Lin A;Khan AH;Eskin E;Horvath S;Lusis AJ;Ophoff RA;Smith DJ
通讯作者：
Smith DJ
影响因子：
11.8
作者：
Ahmed, Mohi;Wong, Elaine Y. M.;Sun, Jianbo;Xu, Jinshu;Wang, Feng;Xu, Pin-Xian
通讯作者：
Xu, Pin-Xian
DOI：
10.1534/g3.115.020784
发表时间：
2015-07-28
期刊：
G3 (Bethesda, Md.)
影响因子：
--
作者：
Rau CD;Parks B;Wang Y;Eskin E;Simecek P;Churchill GA;Lusis AJ
通讯作者：
Lusis AJ
DOI：
10.1523/jneurosci.2845-09.2009
发表时间：
2009-11-11
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kujawa SG;Liberman MC
通讯作者：
Liberman MC