Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss

Dragana Vuckovic, Sally Dawson, Deborah I. Scheffer, Taina Rantanen, Anna Morgan, Mariateresa Di Stazio, Diego Vozzi, Teresa Nutile, Maria P. Concas, Ginevra Biino, Lisa Nolan, Aileen Bahl, Anu Loukola, Anne Viljanen, Adrian Davis, Marina Ciullo, David P. Corey, Mario Pirastu, Paolo Gasparini, Giorgia Girotto

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12 Citations (Scopus)


Hearing loss and individual differences in normal hearing both have a substantial genetic basis. Although many new genes contributing to deafness have been identified, very little is knownabout genes/variants modulating the normal range of hearing ability. To fill this gap, we performed a two-stage meta-analysis on hearing thresholds (tested at 0.25, 0.5, 1, 2, 4, 8 kHz) and on pure-tone averages (low-, medium- and high-frequency thresholds grouped) in several isolated populations from Italy and Central Asia (total N = 2636). Here, we detected two genome-wide significant loci close to PCDH20 and SLC28A3 (top hits: rs78043697, P = 4.71E-10 and rs7032430, P = 2.39E-09, respectively). For both loci, we sought replication in two independent cohorts: B58C from the UK (N = 5892) and FITSA from Finland (N = 270). Both loci were successfully replicated at a nominal level of significance (P < 0.05). In order to confirm our quantitative findings,we carried out RT-PCR and reported RNA-Seq data, which showed that both genes are expressed in mouse inner ear, especially in hair cells, further suggesting them as good candidates for modulatory genes in the auditory system. Sequencing data revealed no functional variants in the coding region of PCDH20 or SLC28A3, suggesting that variation in regulatory sequences may affect expression. Overall, these results contribute to a better understanding of the complex mechanisms underlying human hearing function.

Original languageEnglish
Article numberddv279
Pages (from-to)5655-5664
Number of pages10
JournalHuman Molecular Genetics
Issue number19
Publication statusPublished - 1 Oct 2015
Externally publishedYes


ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Vuckovic, D., Dawson, S., Scheffer, D. I., Rantanen, T., Morgan, A., Di Stazio, M., Vozzi, D., Nutile, T., Concas, M. P., Biino, G., Nolan, L., Bahl, A., Loukola, A., Viljanen, A., Davis, A., Ciullo, M., Corey, D. P., Pirastu, M., Gasparini, P., & Girotto, G. (2015). Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss. Human Molecular Genetics, 24(19), 5655-5664. [ddv279].