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. 2021 Jul 17:2021:3629624.
doi: 10.1155/2021/3629624. eCollection 2021.

A Genome-Wide Association Study of Age-Related Hearing Impairment in Middle- and Old-Aged Chinese Twins

Haiping Duan  1   2   3 , Wanxue Song  1 , Weijing Wang  1 , Hainan Cao  4 , Bingling Wang  2   3 , Yan Liu  2   3 , Chunsheng Xu  2   3 , Yili Wu  1 , Zengchang Pang  2 , Dongfeng Zhang  1
Affiliations

A Genome-Wide Association Study of Age-Related Hearing Impairment in Middle- and Old-Aged Chinese Twins

Haiping Duan et al. Biomed Res Int. .

Abstract

Background: Age-related hearing impairment (ARHI) is considered an unpreventable disorder. We aimed to detect specific genetic variants that are potentially related to ARHI via genome-wide association study (GWAS).

Methods: A sample of 131 dizygotic twins was genotyped for single-nucleotide polymorphism- (SNP-) based GWAS. Gene-based test was performed using VEGAS2. Pathway enrichment analysis was conducted by PASCAL.

Results: The twins are with a median age of 49 years, of which 128 were females and 134 were males. rs6633657 was the only SNP that reached the genome-wide significance level for better ear hearing level (BEHL) at 2.0 kHz (P = 1.19 × 10-8). Totally, 9, 10, 42, 7, 17, and 5 SNPs were suggestive evidence level for (P < 1 × 10-5) BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and pure tone average (PTA), respectively. Several promising genetic regions in chromosomes (near the C20orf196, AQPEP, UBQLN3, OR51B5, OR51I2, OR52D1, GLTP, GIT2, and PARK2) nominally associated with ARHI were identified. Gene-based analysis revealed 165, 173, 77, 178, 170, and 145 genes nominally associated with BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and PTA, respectively (P < 0.05). For BEHLs at 0.5, 1.0, and 2.0 kHz, the main enriched pathways were phosphatidylinositol signaling system, regulation of ornithine decarboxylase, eukaryotic translation initiation factor (EIF) pathway, amine compound solute carrier (SLC) transporters, synthesis of phosphoinositides (PIPS) at the plasma membrane, and phosphatidylinositols (PI) metabolism.

Conclusions: The genetic variations reported herein are significantly involved in functional genes and regulatory domains that mediate ARHI pathogenesis. These findings provide clues for the further unraveling of the molecular physiology of hearing functions and identifying novel diagnostic biomarkers and therapeutic targets of ARHI.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Figure 1
Figure 1
Quantile–quantile plots for GWAS of age-related hearing impairment measured by better ear hearing levels and pure tone average. The x-axis shows the -log10 of expected P values of association from Chi-square distribution, and the y-axis shows the -log10 of P values from the observed Chi-square distribution. Black dots represent the observed data with the top hit single-nucleotide polymorphism (SNP) being colored, and the red line is the expectation under the null hypothesis of no association. Gene at the best SNP is indicated.
Figure 2
Figure 2
Manhattan plots for GWAS of age-related hearing impairment measured by better ear hearing levels (BEHLs) and pure tone average (PTA). The x-axis shows the numbers of autosomes and the X chromosome, and the y-axis shows the -log10 of P values for statistical significance. The dots represent the single-nucleotide polymorphisms (SNPs). Except for the strongest association being detected with rs6633657 (P = 1.19 × 10−8) located on chromosome 23 for BEHL (2.0 kHz), no other SNP reached the genome-wide significance level (P < 5 × 10−8). However, several SNPs were suggestive of association (P < 1 × 10−5) for BEHLs and PTA.
Figure 3
Figure 3
Regional association plots showing strong signals for GWAS of age-related hearing impairment measured by better ear hearing levels (BEHLs) and pure tone average (PTA). (a) BEHL(0.5 kHz), (b) BEHL(1.0 kHz), (c) BEHL(2.0 kHz), (d) BEHL(4.0 kHz), (e) BEHL(8.0 kHz), and (f) PTA.
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