Association of SNPs in LCP1 and CTIF with hearing in 11 year old children: findings from the Avon Longitudinal Study of Parents and Children (ALSPAC) birth cohort and the G-EAR consortium.
BACKGROUND
The genetic basis of hearing loss in humans is relatively poorly understood. In recent years, experimental approaches including laboratory studies of early onset hearing loss in inbred mouse strains, or proteomic analyses of hair cells or hair bundles, have suggested new candidate molecules involved in hearing function. However, the relevance of these genes/gene products to hearing function in humans remains unknown. We investigated whether single nucleotide polymorphisms (SNPs) in the human orthologues of genes of interest arising from the above-mentioned studies correlate with hearing function in children.


METHODS
577 SNPs from 13 genes were each analysed by linear regression against averaged high (3, 4 and 8 kHz) or low frequency (0.5, 1 and 2 kHz) audiometry data from 4970 children in the Avon Longitudinal Study of Parents and Children (ALSPAC) birth-cohort at age eleven years. Genes found to contain SNPs with low p-values were then investigated in 3417 adults in the G-EAR study of hearing.


RESULTS
Genotypic data were available in ALSPAC for a total of 577 SNPs from 13 genes of interest. Two SNPs approached sample-wide significance (pre-specified at p = 0.00014): rs12959910 in CBP80/20-dependent translation initiation factor (CTIF) for averaged high frequency hearing (p = 0.00079, β = 0.61 dB per minor allele); and rs10492452 in L-plastin (LCP1) for averaged low frequency hearing (p = 0.00056, β = 0.45 dB). For low frequencies, rs9567638 in LCP1 also enhanced hearing in females (p = 0.0011, β = -1.76 dB; males p = 0.23, β = 0.61 dB, likelihood-ratio test p = 0.006). SNPs in LCP1 and CTIF were then examined against low and high frequency hearing data for adults in G-EAR. Although the ALSPAC results were not replicated, a SNP in LCP1, rs17601960, is in strong LD with rs9967638, and was associated with enhanced low frequency hearing in adult females in G-EAR (p = 0.00084).


CONCLUSIONS
There was evidence to suggest that multiple SNPs in CTIF may contribute a small detrimental effect to hearing, and that a sex-specific locus in LCP1 is protective of hearing. No individual SNPs reached sample-wide significance in both ALSPAC and G-EAR. This is the first report of a possible association between LCP1 and hearing function.
School of Social and Community Medicine, University of Bristol, Bristol, BS8 2PS, UK. sean.harrison@bristol.ac.uk.
Sean
S
Harrison
School of Social and Community Medicine, University of Bristol, Bristol, BS8 2PS, UK. s.j.lewis@bristol.ac.uk.
Sarah J
SJ
Lewis
School of Social and Community Medicine, University of Bristol, Bristol, BS8 2PS, UK. amanda.hall@bristol.ac.uk.
Amanda J
AJ
Hall
Department of Medical, Surgical and Health Sciences, University of Trieste, 34100, Trieste, Italy. dragana.vuckovic@burlo.trieste.it.
Dragana
D
Vuckovic
Department of Medical, Surgical and Health Sciences, University of Trieste, 34100, Trieste, Italy. giorgia.girotto@burlo.trieste.it.
Giorgia
G
Girotto
School of Social and Community Medicine, University of Bristol, Bristol, BS8 2PS, UK. richard.martin@bristol.ac.uk.
Richard M
RM
Martin
School of Biochemistry, University of Bristol, Bristol, BS8 1TD, UK. jo.adams@bristol.ac.uk.
Josephine C
JC
Adams
D000328:Adult; D000818:Animals; D002648:Child; D015331:Cohort Studies; D039642:Eukaryotic Initiation Factors / Q000235:genetics*; D005260:Female; D056426:Genetic Loci / Q000235:genetics; D005838:Genotype; D006309:Hearing / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007223:Infant; D038622:Internationality; D008137:Longitudinal Studies; D008297:Male; D051379:Mice; D008840:Microfilament Proteins / Q000235:genetics*; D017084:Otoacoustic Emissions, Spontaneous; D036801:Parturition; D020641:Polymorphism, Single Nucleotide; D051381:Rats
C579433:CTIF protein, human; D039642:Eukaryotic Initiation Factors; C047262:LCP1 protein, human; D008840:Microfilament Proteins