The Genetic Contribution of the X Chromosome in Age-related Hearing Loss

Overview

Journal Front Genet

Date 2023 Mar 10

PMID 36896235

Authors

Elnaz Naderi

Diana M Cornejo-Sanchez

Guangyou Li

Isabelle Schrauwen

Gao T Wang

Andrew T DeWan

Suzanne M Leal

Affiliations

Soon will be listed here.

Abstract

Age-related (AR) hearing loss (HL) is the most common sensory impairment with heritability of 55%. The aim of this study was to identify genetic variants on chromosome X associated with ARHL through the analysis of data obtained from the UK Biobank. We performed association analysis between self-reported measures of HL and genotyped and imputed variants on chromosome X from ∼460,000 white Europeans. We identified three loci associated with ARHL with a genome-wide significance level (p < 5 × 10), (rs186256023, = 4.9 × 10) and (rs4370706, = 2.3 × 10) in combined analysis of males and females, and (rs138497700, = 8.9 × 10) in the sex-stratified analysis of males. mRNA expression analysis showed and are expressed in mice and adult human inner ear tissues, particularly in the inner hair cells. We estimated that only a small amount of variation of ARHL, 0.4%, is explained by variants on the X chromosome. This study suggests that although there are likely a few genes contributing to ARHL on the X chromosome, the role that the X chromosome plays in the etiology of ARHL may be limited.

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References

da Silva Souza D, Luckwu B, Andrade W, Pessoa L, Nascimento J, da Rosa M . Variation in the Hearing Threshold in Women during the Menstrual Cycle. Int Arch Otorhinolaryngol. 2017; 21(4):323-328. PMC: 5629086. DOI: 10.1055/s-0037-1598601. View

Kikuchi K, Sakamoto Y, Uezu A, Yamamoto H, Ishiguro K, Shimamura K . Map7D2 and Map7D1 facilitate microtubule stabilization through distinct mechanisms in neuronal cells. Life Sci Alliance. 2022; 5(8). PMC: 9039348. DOI: 10.26508/lsa.202201390. View

Salvi R, Ding D, Jiang H, Chen G, Greco A, Manohar S . Hidden Age-Related Hearing Loss and Hearing Disorders: Current Knowledge and Future Directions. Hearing Balance Commun. 2019; 16(2):74-82. PMC: 6436814. DOI: 10.1080/21695717.2018.1442282. View

Lyon M . Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature. 1961; 190:372-3. DOI: 10.1038/190372a0. View

Hultcrantz M, Simonoska R, Stenberg A . Estrogen and hearing: a summary of recent investigations. Acta Otolaryngol. 2005; 126(1):10-4. DOI: 10.1080/00016480510038617. View

Zhou S, Shi Z, Cui M, Li J, Ma Z, Shi Y . A New Role for LOC101928437 in Non-Syndromic Intellectual Disability: Findings from a Family-Based Association Test. PLoS One. 2015; 10(8):e0135669. PMC: 4545728. DOI: 10.1371/journal.pone.0135669. View

Migeon B . X-linked diseases: susceptible females. Genet Med. 2020; 22(7):1156-1174. PMC: 7332419. DOI: 10.1038/s41436-020-0779-4. View

Kristiansen M, Knudsen G, Bathum L, Naumova A, Sorensen T, Brix T . Twin study of genetic and aging effects on X chromosome inactivation. Eur J Hum Genet. 2005; 13(5):599-606. DOI: 10.1038/sj.ejhg.5201398. View

Shoukat H, Ghous G, Tarar Z, Shoukat M, Ajmal N . Skewed Inactivation of X Chromosome: A Cause of Hemophilia Manifestation in Carrier Females. Cureus. 2020; 12(10):e11216. PMC: 7704156. DOI: 10.7759/cureus.11216. View

10.

Carrel L, Willard H . X-inactivation profile reveals extensive variability in X-linked gene expression in females. Nature. 2005; 434(7031):400-4. DOI: 10.1038/nature03479. View

11.

Schaffner S . The X chromosome in population genetics. Nat Rev Genet. 2004; 5(1):43-51. DOI: 10.1038/nrg1247. View

12.

Doetzlhofer A, White P, Johnson J, Segil N, Groves A . In vitro growth and differentiation of mammalian sensory hair cell progenitors: a requirement for EGF and periotic mesenchyme. Dev Biol. 2004; 272(2):432-47. DOI: 10.1016/j.ydbio.2004.05.013. View

13.

Hooikaas P, Martin M, Muhlethaler T, Kuijntjes G, Peeters C, Katrukha E . MAP7 family proteins regulate kinesin-1 recruitment and activation. J Cell Biol. 2019; 218(4):1298-1318. PMC: 6446838. DOI: 10.1083/jcb.201808065. View

14.

Bowl M, Dawson S . Age-Related Hearing Loss. Cold Spring Harb Perspect Med. 2018; 9(8). PMC: 6671929. DOI: 10.1101/cshperspect.a033217. View

15.

Yuan J, Sun Y, Sang S, Pham J, Kong W . The risk of cognitive impairment associated with hearing function in older adults: a pooled analysis of data from eleven studies. Sci Rep. 2018; 8(1):2137. PMC: 5794920. DOI: 10.1038/s41598-018-20496-w. View

16.

Shen J, Scheffer D, Kwan K, Corey D . SHIELD: an integrative gene expression database for inner ear research. Database (Oxford). 2015; 2015:bav071. PMC: 4513695. DOI: 10.1093/database/bav071. View

17.

McCarthy S, Das S, Kretzschmar W, Delaneau O, Wood A, Teumer A . A reference panel of 64,976 haplotypes for genotype imputation. Nat Genet. 2016; 48(10):1279-83. PMC: 5388176. DOI: 10.1038/ng.3643. View

18.

Smirnov A, Lena A, Cappello A, Panatta E, Anemona L, Bischetti S . ZNF185 is a p63 target gene critical for epidermal differentiation and squamous cell carcinoma development. Oncogene. 2018; 38(10):1625-1638. PMC: 6755960. DOI: 10.1038/s41388-018-0509-4. View

19.

Kolla L, Kelly M, Mann Z, Anaya-Rocha A, Ellis K, Lemons A . Characterization of the development of the mouse cochlear epithelium at the single cell level. Nat Commun. 2020; 11(1):2389. PMC: 7221106. DOI: 10.1038/s41467-020-16113-y. View

20.

Tadros S, Frisina S, Mapes F, Frisina D, Frisina R . Higher serum aldosterone correlates with lower hearing thresholds: a possible protective hormone against presbycusis. Hear Res. 2005; 209(1-2):10-8. DOI: 10.1016/j.heares.2005.05.009. View