Hearing Function: Identification of New Candidate Genes Further Explaining the Complexity of This Sensory Ability



Concas, Maria Pina, Morgan, Anna, Serra, Fabrizio, Nagtegaal, Andries Paul, Oosterloo, Berthe C, Seshadri, Sudha, Heard-Costa, Nancy, Van Camp, Guy, Fransen, Erik, Francescatto, Margherita
et al (show 5 more authors) (2021) Hearing Function: Identification of New Candidate Genes Further Explaining the Complexity of This Sensory Ability. GENES, 12 (8). 1228-.

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Abstract

To date, the knowledge of the genetic determinants behind the modulation of hearing ability is relatively limited. To investigate this trait, we performed Genome-Wide Association Study (GWAS) meta-analysis using genotype and audiometric data (hearing thresholds at 0.25, 0.5, 1, 2, 4, and 8 kHz, and pure-tone averages of thresholds at low, medium, and high frequencies) collected in nine cohorts from Europe, South-Eastern USA, Caucasus, and Central Asia, for an overall number of ~9000 subjects. Three hundred seventy-five genes across all nine analyses were tagged by single nucleotide polymorphisms (SNPs) reaching a suggestive <i>p</i>-value (<i>p</i> < 10<sup>-5</sup>). Amongst these, 15 were successfully replicated using a gene-based approach in the independent Italian Salus in the Apulia cohort (<i>n</i> = 1774) at the nominal significance threshold (<i>p</i> < 0.05). In addition, the expression level of the replicated genes was assessed in published human and mouse inner ear datasets. Considering expression patterns in humans and mice, eleven genes were considered particularly promising candidates for the hearing function: <i>BNIP3L</i>, <i>ELP5</i>, <i>MAP3K20</i>, <i>MATN2</i>, <i>MTMR7, MYO1E</i>, <i>PCNT</i>, <i>R3HDM1</i>, <i>SLC9A9, TGFB2,</i> and <i>YTHDC2</i>. These findings represent a further contribution to our understanding of the genetic basis of hearing function and its related diseases.

Item Type: Article
Uncontrolled Keywords: hearing, GWAS, meta-analysis, inner ear, gene expression
Divisions: Faculty of Health and Life Sciences
Faculty of Health and Life Sciences > Institute of Life Courses and Medical Sciences
Depositing User: Symplectic Admin
Date Deposited: 20 Jan 2022 12:50
Last Modified: 13 Feb 2024 17:13
DOI: 10.3390/genes12081228
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3147266