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

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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 , vol 24 , no. 19 , pp. 5655-5664 . DOI: 10.1093/hmg/ddv279

Title: Genome-wide association analysis on normal hearing function identifies PCDH20 and SLC28A3 as candidates for hearing function and loss
Author: Vuckovic, Dragana; Dawson, Sally; Scheffer, Deborah I.; Rantanen, Taina; Morgan, Anna; Di Stazio, Mariateresa; Vozzi, Diego; Nutile, Teresa; Concas, Maria P.; Biino, Ginevra; Nolan, Lisa; Bahl, Aileen; Loukola, Anu; Viljanen, Anne; Davis, Adrian; Ciullo, Marina; Corey, David P.; Pirastu, Mario; Gasparini, Paolo; Girotto, Giorgia
Other contributor: University of Helsinki, Institute for Molecular Medicine Finland (FIMM)
University of Helsinki, Institute for Molecular Medicine Finland (FIMM)

Publisher: Oxford University Press
Date: 2015-10-01
Language: eng
Number of pages: 10
Belongs to series: Human Molecular Genetics
ISSN: 0964-6906
DOI: http://dx.doi.org/10.1093/hmg/ddv279
URI: http://hdl.handle.net/10138/225080
Abstract: 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 known about 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.
Subject: COMMON DISEASES
MYOSIN-VIIA
LOCI
METAANALYSIS
MICE
VARIANTS
GENOTYPE
SUSCEPTIBILITY
TRANSPORTER-3
LOCALIZATION
3111 Biomedicine
Rights: Creative Commons License (CC BY 3.0)


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