Salt-inducible kinase 3, SIK3, is a new gene associated with hearing

Lisa E. Wolber, Giorgia Girotto, Annalisa Buniello, Dragana Vuckovic, Nicola Pirastu, Beatriz Lorente-Cánovas, Igor Rudan, Caroline Hayward, Ozren Polasek, Marina Ciullo, Massimo Mangino, Claire Steves, Maria P ina Concas, Massilimiliano Cocca, Tim D. Spector, Paolo Gasparini, Karen P. Steel, Frances M K Williams

Research output: Contribution to journalArticle

Abstract

Hearing function is known to be heritable, but few significant and reproducible associations of genetic variants have been identified to date in the adult population. In this study, genome-wide association results of hearing function from the G-EAR consortium and TwinsUK were used for meta-analysis. Hearing ability in eight population samples of Northern and Southern European ancestry (n = 4591) and the Silk Road (n = 348) was measured using pure-tone audiometry and summarized using principal component (PC) analysis. Genome-wide association analyses for PC1-3 were conducted separately in each sample assuming an additive model adjusted for age, sex and relatedness of subjects. Meta-analysis was performed using 2.3 million single-nucleotide polymorphisms (SNPs) tested against each of the three PCs of hearing ability in 4939 individuals. A single SNP lying in intron 6 of the salt-inducible kinase 3 (SIK3) gene was found to be associated with hearing PC2 (P = 3.7×10(-8)) and further supported by whole-genome sequence in a subset. To determine the relevance of this gene in the ear, expression of the Sik3 protein was studied in mouse cochlea of different ages. Sik3 was expressed in murine hair cells during early development and in cells of the spiral ganglion during early development and adulthood. Our results suggest a developmental role of Sik3 in hearing and may be required for the maintenance of adult auditory function.

Original languageEnglish
Pages (from-to)6407-6418
Number of pages12
JournalHuman Molecular Genetics
Volume23
Issue number23
DOIs
Publication statusPublished - Dec 1 2014

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Hearing
Phosphotransferases
Salts
Genes
Aptitude
Single Nucleotide Polymorphism
Meta-Analysis
Genome
Spiral Ganglion
Pure-Tone Audiometry
Silk
Genome-Wide Association Study
Cochlea
Principal Component Analysis
Introns
Population
Ear
Maintenance
Proteins

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Wolber, L. E., Girotto, G., Buniello, A., Vuckovic, D., Pirastu, N., Lorente-Cánovas, B., ... Williams, F. M. K. (2014). Salt-inducible kinase 3, SIK3, is a new gene associated with hearing. Human Molecular Genetics, 23(23), 6407-6418. https://doi.org/10.1093/hmg/ddu346

Salt-inducible kinase 3, SIK3, is a new gene associated with hearing. / Wolber, Lisa E.; Girotto, Giorgia; Buniello, Annalisa; Vuckovic, Dragana; Pirastu, Nicola; Lorente-Cánovas, Beatriz; Rudan, Igor; Hayward, Caroline; Polasek, Ozren; Ciullo, Marina; Mangino, Massimo; Steves, Claire; Concas, Maria P ina; Cocca, Massilimiliano; Spector, Tim D.; Gasparini, Paolo; Steel, Karen P.; Williams, Frances M K.

In: Human Molecular Genetics, Vol. 23, No. 23, 01.12.2014, p. 6407-6418.

Research output: Contribution to journalArticle

Wolber, LE, Girotto, G, Buniello, A, Vuckovic, D, Pirastu, N, Lorente-Cánovas, B, Rudan, I, Hayward, C, Polasek, O, Ciullo, M, Mangino, M, Steves, C, Concas, MPI, Cocca, M, Spector, TD, Gasparini, P, Steel, KP & Williams, FMK 2014, 'Salt-inducible kinase 3, SIK3, is a new gene associated with hearing', Human Molecular Genetics, vol. 23, no. 23, pp. 6407-6418. https://doi.org/10.1093/hmg/ddu346
Wolber LE, Girotto G, Buniello A, Vuckovic D, Pirastu N, Lorente-Cánovas B et al. Salt-inducible kinase 3, SIK3, is a new gene associated with hearing. Human Molecular Genetics. 2014 Dec 1;23(23):6407-6418. https://doi.org/10.1093/hmg/ddu346
Wolber, Lisa E. ; Girotto, Giorgia ; Buniello, Annalisa ; Vuckovic, Dragana ; Pirastu, Nicola ; Lorente-Cánovas, Beatriz ; Rudan, Igor ; Hayward, Caroline ; Polasek, Ozren ; Ciullo, Marina ; Mangino, Massimo ; Steves, Claire ; Concas, Maria P ina ; Cocca, Massilimiliano ; Spector, Tim D. ; Gasparini, Paolo ; Steel, Karen P. ; Williams, Frances M K. / Salt-inducible kinase 3, SIK3, is a new gene associated with hearing. In: Human Molecular Genetics. 2014 ; Vol. 23, No. 23. pp. 6407-6418.
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