A Novel Z-Score–Based Method to Analyze Candidate Genes for Age-Related Hearing Impairment

Fransén, Erik; Laer, Lut Van; Lemkens, Nele; Caethoven, Goele; Flothmann, Kris; Govaerts, Paul; Heyning, Paul Van de; Camp, Guy Van

doi:10.1097/01.aud.0000120362.69077.0b

Cited by 26 publications

(27 citation statements)

References 23 publications

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“…Frequency-specific thresholds were converted to sex-and ageindependent Z-scores based on the ISO 7029 standards [International Organisation for Standardisation, 2000;Fransen et al, 2004]. The Z-score is defined as the number of standard deviations the hearing threshold differs from the median value at a specific frequency.…”

Section: Materials and Methods Calculating Z-scoresmentioning

confidence: 99%

KCNQ4: a gene for age-related hearing impairment?

et al. 2006

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Age-related hearing impairment (ARHI) is the most common sensory impairment among the elderly. It is a complex disorder influenced by genetic as well as environmental factors. SNPs in a candidate susceptibility gene, KCNQ4, were examined in two independent Caucasian populations. Two quantitative trait locus (QTL) values were investigated: Zhigh and Zlow, a measure of high and respectively low frequency hearing loss. In the first population, the statistical analysis of 23 genotyped SNPs spread across KCNQ4 resulted in significant p-values for two SNPs for Zhigh-SNP9 (NT_004511:g.11244177A > T) and SNP15 (NT_004511:g.11257005C > T; NP_004691:p.Ala259Ala), and one SNP for Zlow-SNP12 (NT_004511:g.11249550A > T). The linkage disequilibrium (LD) structure of KCNQ4 was subsequently determined in a 34-kb region surrounding the significant SNPs, resulting in three LD-blocks. LD-block 1 contains SNP9 and covers an area of 5 kb, LD-block 2 measures 5 kb and surrounds SNP13 (NT_004511:g.11253513A > G) to SNP18 (NT_004511:g.11257509G > A; NP_004691:p.Thr293Thr), and LD-block 3 spans 7 kb. Five tag-SNPs of block 1 and 2, and 2 extra SNPs were subsequently genotyped in the second population. Again, several SNPs were positively associated with ARHI: one SNP (SNP18) for the high frequencies and three SNPs (SNP9, SNP12, and SNP18) for the low frequencies, although only a single SNP (SNP12) resulted in significant p-values in both populations. Nevertheless, the associated SNPs of both populations were all located in the same 13-kb region in the middle of the KCNQ4 gene.

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Section: Materials and Methods Calculating Z-scoresmentioning

confidence: 99%

KCNQ4: a gene for age-related hearing impairment?

et al. 2006

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“…Van Laer et al [70] reported two independent association studies, using two non-synomous SNPs within the DFNA5 gene, to investigate its possible involvement in ARHL, but no allelic or genotypic association was detected. In another study, Fransen et al [71] define a quantitative trait (QT) value, correcting for age and gender, to allow the genetic study of ARHL as a QT. No association was found; however, this approach may improve the power to detect genes with small to medium effects and circumvents the difficulty of assigning case and control status to what is a continuous trait.…”

Section: Association Studiesmentioning

confidence: 99%

Ageing and hearing loss

Yan

2007

The Journal of Pathology

270

188

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Although many adults retain good hearing as they age, hearing loss associated with ageing is common among elderly persons. There are a number of pathophysiolological processes underlying age-related changes to functional components in the inner ear. Genetic factors determine the ageing process but are under the influence of intrinsic and environmental factors. It is difficult to distinguish changes of normal ageing from those of other contributing factors. The effects of age-related deafness can have significant physical, functional and mental health consequences. Although a deficit in hearing can be corrected to some degree by a hearing aid or other appropriate amplification devices, hearing-related rehabilitative needs are much more than simply amplifying external sound. Only by better understanding the process of ageing and its effect on the auditory function can we better accommodate elderly people in our day-to-day interactions. We review here the structure and function of the inner ear, pathophysiology associated with age-related hearing loss (ARHL), heritability, allelism and modifier genes of ARHL, and evaluate the genetic analyses for identification of genetic factors that are involved.

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“…A disadvantage of treating ARHI as a dichotomous trait (affected/unaffected) is the loss of statistical power, as generally information is lost when a quantitative trait such as ARHI is dichotomized [Page and Amos, 1999]. Fransen et al [2004] proposed the calculation of a Zscore to enable treatment of ARHI as a quantitative trait. This Z-score is an age-and gender-independent value, based upon the ISO 7029 standard [Fransen et al, 2004].…”

Section: How To Analyze Genetic Factors Involved In Human Arhimentioning

confidence: 99%

“…Fransen et al [2004] proposed the calculation of a Zscore to enable treatment of ARHI as a quantitative trait. This Z-score is an age-and gender-independent value, based upon the ISO 7029 standard [Fransen et al, 2004]. Using this approach, random samples genotyped for a particular SNP in a candidate gene can be grouped according to their genotype and subsequently statistically analyzed using ANOVA-based methods.…”

Section: How To Analyze Genetic Factors Involved In Human Arhimentioning

confidence: 99%

The Complexity of Age-Related Hearing Impairment: Contributing Environmental and Genetic Factors

Eyken¹,

Camp²,

Laer³

2007

Audiol Neurotol

261

205

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Age-related hearing impairment (ARHI) is the most common sensory impairment seen in the elderly. It is a complex disorder, with both environmental as well as genetic factors contributing to the impairment. The involvement of several environmental factors has been partially elucidated. A first step towards the identification of the genetic factors has been made, which will result in the identification of susceptibility genes, and will provide possible targets for the future treatment and/or prevention of ARHI. This paper aims to give a broad overview of the scientific findings related to ARHI, focusing mainly on environmental and genetic data in humans and in animal models. In addition, methods for the identification of contributing genetic factors as well as possible future therapeutic strategies are discussed.

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A Novel Z-Score–Based Method to Analyze Candidate Genes for Age-Related Hearing Impairment

Abstract: The Z-score conversion appears to be a valid method to describe to what extent a subject is affected by ARHI, allowing to compare persons from different age and gender. This method can be the basis of future, powerful studies to identify ARHI genes.

Cited by 26 publications

References 23 publications

KCNQ4: a gene for age-related hearing impairment?

KCNQ4: a gene for age-related hearing impairment?

Ageing and hearing loss

The Complexity of Age-Related Hearing Impairment: Contributing Environmental and Genetic Factors

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