Dataset Information

Hearing ability with age in northern European women: a new web-based approach to genetic studies.

ABSTRACT: Age-related hearing impairment (ARHI) affects 25-40% of individuals over the age of 65. Despite the high prevalence of this complex trait, ARHI is still poorly understood. We hypothesized that variance in hearing ability with age is largely determined by genetic factors. We collected audiologic data on females of Northern European ancestry and compared different audiogram representations. A web-based speech-to-noise ratio (SNR) hearing test was compared with pure-tone thresholds to see if we could determine accurately hearing ability on people at home and the genetic contribution to each trait compared. Volunteers were recruited from the TwinsUK cohort. Hearing ability was determined using pure-tone audiometry and a web-based hearing test. Different audiogram presentations were compared for age-correlation and reflection of audiogram shape. Using structural equation modelling based on the classical twin model the heritability of ARHI, as measured by the different phenotypes, was estimated and shared variance between the web-based SNR test and pure-tone audiometry determined using bivariate modelling. Pure-tone audiometric data was collected on 1033 older females (age: 41-86). 1970 volunteers (males and females, age: 18-85) participated in the SNR. In the comparison between different ARHI phenotypes the difference between the first two principle components (PC1-PC2) best represented ARHI. The SNR test showed a sensitivity and specificity of 89% and 80%, respectively, in comparison with pure-tone audiogram data. Univariate heritability estimates ranged from 0.70 (95% CI: 0.63-0.76) for (PC1-PC2) to 0.56 (95% CI: 0.48-0.63) for PC2. The genetic correlation of PC1-PC2 and SNR was -0.67 showing that the 2 traits share variances attributed to additive genetic factors. Hearing ability showed considerable heritability in our sample. We have shown that the SNR test provides a useful surrogate marker of hearing. This will enable a much larger sample to be collected at a fraction of the cost, facilitating future genetic association studies.

SUBMITTER: Wolber LE

PROVIDER: S-EPMC3340381 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Epigenetic regulation of gene expression has been shown to change over time and may be associated with environmental exposures in common complex traits. Age-related hearing impairment is a complex disorder, known to be heritable, with heritability estimates of 57-70%. Epigenetic regulation might explain the observed difference in age of onset and magnitude of hearing impairment with age. Epigenetic epidemiology studies using unrelated samples can be limited in their ability to detect small effects, and recent epigenetic findings in twins underscore the power of this well matched study design. We investigated the association between venous blood DNA methylation epigenome-wide and hearing ability. Pure-tone audiometry (PTA) and Illumina HumanMethylation array data were obtained from female twin volunteers enrolled in the TwinsUK register. Two study groups were explored: first, an epigenome-wide association scan (EWAS) was performed in a discovery sample (n=115 subjects, age range: 47-83 years, Illumina 27 k array), then replication of the top ten associated probes from the discovery EWAS was attempted in a second unrelated sample (n=203, age range: 41-86 years, Illumina 450 k array). Finally, a set of monozygotic (MZ) twin pairs (n = 21 pairs) within the discovery sample (Illumina 27 k array) was investigated in more detail in an MZ discordance analysis. Hearing ability was strongly associated with DNA methylation levels in the promoter regions of several genes, including TCF25 (cg01161216, p = 6.6 × 10(-6)), FGFR1 (cg15791248, p = 5.7 × 10(-5) and POLE (cg18877514, p= 6.3 × 10(-5)). Replication of these results in a second sample confirmed the presence of differential methylation at TCF25 (p(replication)=6 × 10(-5)) and POLE (p(replication)?=0.016). In the MZ discordance analysis, twins' intrapair difference in hearing ability correlated with DNA methylation differences at ACP6 (cg01377755, r=?-0.75, p=1.2 × 10(-4)) and MEF2D (cg08156349, r=?-0.75, p=1.4 × 10(-4)). Examination of gene expression in skin, suggests an influence of differential methylation on expression, which may account for the variation in hearing ability with age.

Project description:BackgroundThe pregnancy rate after cancer treatment for female survivors is lower than that of the general population. Future infertility is a significant concern for patients with breast cancer and is associated with a poor quality of life. Reproductive-age patients with breast cancer have safe options when choosing a type of fertility preservation method to be applied. Better information and support resources aimed at women to support their decision making are needed.ObjectiveThe objective of this study was to develop a web-based shared decision-making tool for helping patients with breast cancer make decisions on fertility preservation.MethodsWe used the action research cycle of observing, reflecting, planning, and acting to develop a web-based shared decision-making tool. The following four phrases were applied: (1) observe and reflect-collect and analyze the decision-making experiences of patients and health care providers; (2) reflect and plan-apply the initial results to create a paper design and modify the content; (3) plan and act-brainstorm about the web pages and modify the content; (4) act and observe-evaluate the effectiveness and refine the website's shared decision-making tool. Interviews, group meetings, and constant dialogue were conducted between the various participants at each step. Effectiveness was evaluated using the Preparation for Decision-Making scale.ResultsFive major parts were developed with the use of the action research approach. The Introduction (part 1) describes the severity of cancer treatment and infertility. Options (part 2) provides the knowledge of fertility preservation. The shared decision-making tool was designed as a step-by-step process (part 3) that involves the comparison of options, patient values, and preferences; their knowledge regarding infertility and options; and reaching a collective decision. Resources (part 4) provides information on the hospitals that provide such services, and References (part 5) lists all the literature cited in the website. The results show the web-based shared decision-making meets both patients' and health providers' needs and helps reproductive-age patients with breast cancer make decisions about fertility preservation.ConclusionsWe have created the first web-based shared decision-making tool for making fertility preservation decisions in Taiwan. We believe female patients of reproductive age will find the tool useful and its use will become widespread, which should increase patient autonomy and improve communication about fertility preservation with clinicians.Trial registrationClinicaltrials.gov NCT04602910; https://clinicaltrials.gov/ct2/show/NCT04602910.

Dataset Information

Hearing ability with age in northern European women: a new web-based approach to genetic studies.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets