| 1. |
- Fransen, Erik, et al.
(author)
-
Occupational Noise, Smoking, and a High Body Mass Index are Risk Factors for Age-related Hearing Impairment and Moderate Alcohol Consumption is Protective : A European Population-based Multicenter Study
- 2008
-
In: Journal of the Association for Research in Otolaryngology. - : Springer. - 1525-3961 .- 1438-7573. ; 9:3, s. 264-276
-
Journal article (peer-reviewed)abstract
- A multicenter study was set up to elucidate the environmental and medical risk factors contributing to age-related hearing impairment (ARHI). Nine subsamples, collected by nine audiological centers across Europe, added up to a total of 4,083 subjects between 53 and 67 years. Audiometric data (pure-tone average [PTA]) were collected and the participants filled out a questionnaire on environmental risk factors and medical history. People with a history of disease that could affect hearing were excluded. PTAs were adjusted for age and sex and tested for association with exposure to risk factors. Noise exposure was associated with a significant loss of hearing at high sound frequencies (>1 kHz). Smoking significantly increased high-frequency hearing loss, and the effect was dose-dependent. The effect of smoking remained significant when accounting for cardiovascular disease events. Taller people had better hearing on average with a more pronounced effect at low sound frequencies (<2 kHz). A high body mass index (BMI) correlated with hearing loss across the frequency range tested. Moderate alcohol consumption was inversely correlated with hearing loss. Significant associations were found in the high
|
|
| 2. |
- Hannula, Samuli, et al.
(author)
-
Audiogram configurations among older adults: Prevalence and relation to self-reported hearing problems
- 2011
-
In: International Journal of Audiology. - : Informa Healthcare. - 1499-2027 .- 1708-8186. ; 50:11, s. 793-801
-
Journal article (peer-reviewed)abstract
- Objective : There are only a few population-based epidemiological studies on audiogram configurations among adults. The aim of this study was to investigate the prevalence of different audiogram configurations among older adults. In addition, audiogram configurations among subjects reporting hearing problems were examined. Design : Cross-sectional, population-based, unscreened epidemiological study among older adults. Study sample : The subjects (850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. Results : The most prevalent audiogram configuration among men was high-frequency steeply sloping (65.3% left ear, 51.2% right ear) and among women, high-frequency gently sloping (33.0% left ear, 31.5% right ear). There were significantly more flat configurations among women than among men. Unclassified audiograms were common especially among women (17.5%). Subjects reporting hearing difficulties, difficulties in following conversation in noise, or tinnitus, more often had a high-frequency steeply sloping configuration than those not reporting. Conclusions : High-frequency sloping audiogram configurations were common among older adults, and a high-frequency steeply sloping configuration was common among those reporting hearing problems.
|
|
| 3. |
- Hannula, Samuli, et al.
(author)
-
Ear diseases and other risk factors for hearing impairment among adults: An epidemiological study
- 2012
-
In: International Journal of Audiology. - : Informa Healthcare. - 1499-2027 .- 1708-8186. ; 51:11, s. 833-840
-
Journal article (peer-reviewed)abstract
- Objective: To investigate the prevalence of ear diseases, other otological risk factors potentially affecting hearing, and noise exposure among adults. Furthermore, subject-related factors possibly associated with hearing impairment (HI), i.e. handedness, eye color, and susceptibility to sunburn, were studied. Design: A cross-sectional, unscreened, population-based, epidemiological study among adults. Study sample: The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. Results: Chronic middle-ear disease (both active and inactive) was the most common ear disease with a prevalence of 5.3%, while the prevalence of otosclerosis was 1.3%, and that of Menieres disease, 0.7%. Noise exposure was reported by 46% of the subjects, and it had no effect on hearing among those with no ear disease or other otological risk factors for HI. Dark eye color and non-susceptibility to sunburn were associated with HI among noise-exposed subjects. Conclusions: Common ear diseases and other otological risk factors constitute a major part of the etiologies of HI among adults. Contrary to previous studies, noise exposure turned out to have only marginal effect on hearing among those with no otological risk factors.
|
|
| 4. |
- Hannula, Samuli, et al.
(author)
-
Hearing in a 54-to 66-year-old population in northern Finland
- 2010
-
In: INTERNATIONAL JOURNAL OF AUDIOLOGY. - : Informa Healthcare. - 1499-2027 .- 1708-8186. ; 49:12, s. 920-927
-
Journal article (peer-reviewed)abstract
- There are only a few large, population-based epidemiological studies on hearing impairment (HI) in adults. The objective of this study was to investigate the prevalence of HI and possible differences between ears in older adults. The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed. Another questionnaire was mailed to collect information on non-participants. The prevalence of HI averaged over the frequencies of 0.5, 1, 2, and 4 kHz for the better ear andgt;= 20 dB HL was 26.7% (men: 36.8%, women: 18.4%). There was no difference between left and right ear pure-tone averages over the frequencies 0.5, 1, 2, and 4 kHz (PTA (0.5-4 kHz)), but a significant difference of -0.8 dB HL was found for the low frequencies 0.125, 0.25, and 0.5 kHz (PTA (0.125-0.5 kHz)), and 4.4 dB HL for the high frequencies over 4, 6, and 8 kHz (PTA (4-8 kHz)). In conclusion, HI was a highly prevalent finding in this age group.
|
|
| 5. |
- Hannula, Samuli, et al.
(author)
-
Self-Reported Hearing Problems among Older Adults: Prevalence and Comparison to Measured Hearing Impairment
- 2011
-
In: JOURNAL OF THE AMERICAN ACADEMY OF AUDIOLOGY. - : American Academy of Audiology. - 1050-0545 .- 2157-3107. ; 22:8, s. 550-559
-
Journal article (peer-reviewed)abstract
- Background: There are not many population-based epidemiological studies on the association between self-reported hearing problems and measured hearing thresholds in older adults. Previous studies have shown that the relationship between self-reported hearing difficulties and measured hearing thresholds is unclear and, according to our knowledge, there are no previous population-based studies reporting hearing thresholds among subjects with hyperacusis. less thanbrgreater than less thanbrgreater thanPurpose: The aim was to investigate the prevalence of self-reported hearing problems, that is, hearing difficulties, difficulties in following a conversation in noise, tinnitus, and hyperacusis, and to compare the results with measured hearing thresholds in older adults. less thanbrgreater than less thanbrgreater thanResearch Design: Cross-sectional, population-based, and unscreened. less thanbrgreater than less thanbrgreater thanStudy Sample: Random sample of subjects (n = 850) aged 54-66 yr living in the city of Oulu (Finland) and the surrounding areas. less thanbrgreater than less thanbrgreater thanData Collection and Analysis: Otological examination, pure tone audiometry, questionnaire survey less thanbrgreater than less thanbrgreater thanResults: The prevalence of self-reported hearing problems was 37.1% for hearing difficulties, 43.3% for difficulties in following a conversation in noise, 29.2% for tinnitus, and 17.2% for hyperacusis. More than half of the subjects had no hearing impairment, or HI (BEHL[better ear hearing level](0.5-4 kHz) andlt; 20 dB HL) even though they reported hearing problems. Subjects with self-reported hearing problems, including tinnitus and hyperacusis, had significantly poorer hearing thresholds than those who did not report hearing problems. Self-reported hearing difficulties predicted hearing impairment in the pure-tone average at 4, 6, and 8 kHz, and at the single frequency of 4 kHz. less thanbrgreater than less thanbrgreater thanConclusions: The results indicate that self-reported hearing difficulties are more frequent than hearing impairment defined by audiometric measurement. Furthermore, self-reported hearing difficulties seem to predict hearing impairment at high frequencies (4-8 kHz) rather than at the frequencies of 0.5-4 kHz, which are commonly used to define the degree of hearing impairment in medical and legal issues.
|
|
| 6. |
- Hendrickx, Jan-Jaap, et al.
(author)
-
Familial aggregation of pure tone hearing thresholds in an aging European population
- 2013
-
In: Otology and Neurotology. - : Lippincott Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 34:5, s. 838-844
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the familial correlations and intraclass correlation of age-related hearing impairment (ARHI) in specific frequencies. In addition, heritability estimates were calculated.STUDY DESIGN: Multicenter survey in 8 European centers.SUBJECTS: One hundred ninety-eight families consisting of 952 family members, screened by otologic examination and structured interviews. Subjects with general conditions, known to affect hearing thresholds or known otologic cause were excluded from the study.RESULTS: We detected familial correlation coefficients of 0.36, 0.37, 0.36, and 0.30 for 0.25, 0.5, 1, and 2 kHz, respectively, and correlation coefficients of 0.20 and 0.18 for 4 and 8 kHz, respectively. Variance components analyses showed that the proportion of the total variance attributable to family differences was between 0.32 and 0.40 for 0.25, 0.5, 1, and 2 kHz and below 0.20 for 4 and 8 kHz. When testing for homogeneity between sib pair types, we observed a larger familial correlation between female than male subjects. Heritability estimates ranged between 0.79 and 0.36 across the frequencies.DISCUSSION: Our results indicate that there is a substantial shared familial effect in ARHI. We found that familial aggregation of ARHI is markedly higher in the low frequencies and that there is a trend toward higher familial aggregation in female compared with male subjects.
|
|
| 7. |
- Hendrickx, Jan-Jaap, et al.
(author)
-
Familial aggregation of tinnitus : a European multicentre study
- 2007
-
In: B-ENT. - Louvain, Belgium : Societe Royale Belge d'Oto - Rhino - Laryngologie et de Chirurgie Cervico - Faciale. - 0001-6497. ; 3:Suppl 7, s. 51-60
-
Journal article (other academic/artistic)abstract
- INTRODUCTION AND AIM:Tinnitus is a common condition affecting approximately 20% of the older population. There is increasing evidence that changes in the central auditory system following cochlear malfunctioning are responsible for tinnitus. To date, few investigators have studied the influence of genetic factors on tinnitus. The present report investigates the presence of a familial effect in tinnitus subjects.METHODS:In a European multicentre study, 198 families were recruited in seven European countries. Each family had at least 3 siblings. Subjects were screened for causes of hearing loss other than presbyacusis by clinical examination and a questionnaire. The presence of tinnitus was evaluated with the question "Nowadays, do you ever get noises in your head or ear (tinnitus) which usually last longer than five minutes". Familial aggregation was tested using three methods: a mixed model approach, calculating familial correlations, and estimating the risk of a subject having tinnitus if the disorder is present in another family member.RESULTS:All methods demonstrated a significant familial effect for tinnitus. The effect persisted after correction for the effect of other risk factors such as hearing loss, gender and age. The size of the familial effect is smaller than that for age-related hearing impairment, with a familial correlation of 0.15.CONCLUSION:The presence of a familial effect for tinnitus opens the door to specific studies that can determine whether this effect is due to a shared familial environment or the involvement of genetic factors. Subsequent association studies may result in the identification of the factors responsible. In addition, more emphasis should be placed on the effect of role models in the treatment of tinnitus.
|
|
| 8. |
- Huyghe, Jeroen R, et al.
(author)
-
A genome-wide analysis of population structure in the Finnish Saami with implications for genetic association studies
- 2011
-
In: EUROPEAN JOURNAL OF HUMAN GENETICS. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 19:3, s. 347-352
-
Journal article (peer-reviewed)abstract
- The understanding of patterns of genetic variation within and among human populations is a prerequisite for successful genetic association mapping studies of complex diseases and traits. Some populations are more favorable for association mapping studies than others. The Saami from northern Scandinavia and the Kola Peninsula represent a population isolate that, among European populations, has been less extensively sampled, despite some early interest for association mapping studies. In this paper, we report the results of a first genome-wide SNP-based study of genetic population structure in the Finnish Saami. Using data from the HapMap and the human genome diversity project (HGDP-CEPH) and recently developed statistical methods, we studied individual genetic ancestry. We quantified genetic differentiation between the Saami population and the HGDP-CEPH populations by calculating pair-wise F-ST statistics and by characterizing identity-by-state sharing for pair-wise population comparisons. This study affirms an east Asian contribution to the predominantly European-derived Saami gene pool. Using model-based individual ancestry analysis, the median estimated percentage of the genome with east Asian ancestry was 6% (first and third quartiles: 5 and 8%, respectively). We found that genetic similarity between population pairs roughly correlated with geographic distance. Among the European HGDP-CEPH populations, F-ST was smallest for the comparison with the Russians (F-ST=0.0098), and estimates for the other population comparisons ranged from 0.0129 to 0.0263. Our analysis also revealed fine-scale substructure within the Finnish Saami and warns against the confounding effects of both hidden population structure and undocumented relatedness in genetic association studies of isolated populations.
|
|
| 9. |
- Huyghe, Jeroen R., et al.
(author)
-
Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami
- 2010
-
In: European Journal of Human Genetics. - : Nature Publishing Group. - 1018-4813 .- 1476-5438. ; 18:5, s. 569-574
-
Journal article (peer-reviewed)abstract
- The Saami from Fennoscandia are believed to represent an ancient, genetically isolated population with no evidence of population expansion. Theoretical work has indicated that under this demographic scenario, extensive linkage disequilibrium (LD) is generated by genetic drift. Therefore, it has been suggested that the Saami would be particularly suited for genetic association studies, offering a substantial power advantage and allowing more economic study designs. However, no study has yet assessed this claim. As part of a GWAS for a complex trait, we evaluated the relative power for association studies of common variants in the Finnish Saami. LD patterns in the Saami were very similar to those in the non-African HapMap reference panels. Haplotype diversity was reduced and, on average, levels of LD were higher in the Saami as compared with those in the HapMap panels. However, using a 'hidden' SNP approach we show that this does not translate into a power gain in association studies. Contrary to earlier claims, we show that for a given set of common SNPs, genomic coverage attained in the Saami is similar to that in the non-African HapMap panels. Nevertheless, the reduced haplotype diversity could potentially facilitate gene identification, especially if multiple rare variants play a role in disease etiology. Our results further indicate that the HapMap is a useful resource for genetic studies in the Saami.
|
|
| 10. |
- Huyghe, Jeroen R., et al.
(author)
-
Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait
- 2008
-
In: American Journal of Human Genetics. - : Cell Press. - 0002-9297 .- 1537-6605. ; 83:3, s. 401-407
-
Journal article (peer-reviewed)abstract
- Age-related hearing impairment (ARHI), or presbycusis, is a very common multifactorial disorder. Despite the knowledge that genetics play an important role in the etiology of human ARHI as revealed by heritability studies, to date, its precise genetic determinants remain elusive. Here we report the results of a cross-sectional family-based genetic study employing audiometric data. By using principal component analysis, we were able to reduce the dimensionality of this multivariate phenotype while capturing most of the variation and retaining biologically important features of the audiograms. We conducted a genome-wide association as well as a linkage scan with high-density SNP microarrays. Because of the presence of genetic population substructure, association testing was stratified after which evidence was combined by meta-analysis. No association signals reaching genome-wide significance were detected. Linkage analysis identified a linkage peak on 8q24.13-q24.22 for a trait correlated to audiogram shape. The signal reached genome-wide significance, as assessed by simulations. This finding represents the first locus for an ARHI trait.
|
|
| 11. |
- Kytövuori, Laura, et al.
(author)
-
A nonsynonymous mutation in the WFS1 gene in a Finnish family with age-related hearing impairment
- 2017
-
In: Hearing Research. - Amsterdam, Netherlands : Elsevier. - 0378-5955 .- 1878-5891. ; 355, s. 97-101
-
Journal article (peer-reviewed)abstract
- Wolfram syndrome (WS) is caused by recessive mutations in the Wolfram syndrome 1 (WFS1) gene. Sensorineural hearing impairment (HI) is a frequent feature in WS and, furthermore, certain mutations in WFS1 cause nonsyndromic dominantly inherited low-frequency sensorineural HI. These two phenotypes are clinically distinct indicating that WFS1 is a reasonable candidate for genetic studies in patients with other phenotypes of HI. Here we have investigated, whether the variation in WFS1 has a pathogenic role in age-related hearing impairment (ARHI). WFS1 gene was investigated in a population sample of 518 Finnish adults born in 1938-1949 and representing variable hearing phenotypes. Identified variants were evaluated with respect to pathogenic potential. A rare mutation predicted to be pathogenic was found in a family with many members with impaired hearing. Twenty members were recruited to a segregation study and a detailed clinical examination. Heterozygous p.Tyr528His variant segregated completely with late-onset HI in which hearing deteriorated first at high frequencies and progressed to mid and low frequencies later in life. We report the first mutation in the WFS1 gene causing late-onset HI with audiogram configurations typical for ARHI. Monogenic forms of ARHI are rare and our results add WFS1 to the short list of such genes.
|
|
| 12. |
- Lohi, Venla, et al.
(author)
-
Hearing impairment among adults : the impact of cardiovascular diseases and cardiovascular risk factors
- 2015
-
In: International Journal of Audiology. - : Taylor & Francis. - 1499-2027 .- 1708-8186. ; 54:4, s. 265-73
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To investigate the influence of cardiovascular diseases on hearing impairment (HI) among adults. Furthermore, to seek other potential risk factors for HI, such as smoking, obesity, and socioeconomic class.DESIGN: A cross-sectional, unscreened, population-based, epidemiological study among adults.STUDY SAMPLE: The subjects (n = 850), aged 54-66 years, were randomly sampled from the population register. A questionnaire survey, an otological examination, and pure-tone audiometry were performed.RESULTS: Cardiovascular diseases did not increase the risk for HI in a propensity-score adjusted logistic regression model: OR 1.24, 95% CI 0.79 to 1.96 for HI defined by better ear hearing level (BEHL), and OR 1.48, 95% CI 0.96 to 2.28 for HI defined by worse ear hearing level (WEHL), in the 0.5-4 kHz frequency range. Heavy smoking is a risk factor for HI among men (BEHL: OR 1.96, WEHL: OR 1.88) and women (WEHL: OR 2.4). Among men, obesity (BEHL, OR 1.85) and lower socioeconomic class (BEHL: OR 2.79, WEHL: OR 2.28) are also risk factors for HI.CONCLUSION: No significant association between cardiovascular disease and HI was found.
|
|
| 13. |
- Lohi, Venla, et al.
(author)
-
Hearing impairment is common among Saami adults in Northern Finland
- 2017
-
In: International Journal of Circumpolar Health. - : Taylor & Francis. - 1239-9736 .- 2242-3982. ; 76:1
-
Journal article (peer-reviewed)abstract
- The Saami are the only indigenous population in Europe and their traditional living area is northern Scandinavia. Hearing impairment (HI) among Saami has not been studied before. The objective was to investigate the presence and type of HI among Saami adults, aged 49-77 years (median age 61 years), living in northern Finland. In addition, the presence of self-reported hearing difficulties, difficulties to hear in background noise and tinnitus were studied. An epidemiological, cross-sectional study encompassing a structured interview, otological examination and audiometry was performed. Bilateral HI was present in 42.9% of men and 29.4% of women, when HI was defined as a pure tone average (PTA) of at least 20 dB hearing level (HL) or more at the frequencies of 0.5, 1, 2 and 4 kHz. In one or both ears (worse ear hearing level, WEHL0.5,1,2,4≥20 dB HL) HI was present in 61.8% of men and 42.2% of women. Sensorineural high frequency hearing impairment was found to be most common. Nearly half (46.9%) of the study subjects reported hearing problems and more than half (55.6%) reported difficulties in following conversation in background noise. Measured HI and subjective hearing difficulties are common among the Saami adults. The healthcare personnel working in this area should be aware of the hearing problems of the Saami population.ABBREVIATIONS: ARHI, Age-related hearing impairment; PTA, Pure tone average; HI, Hearing impairment; HL, Hearing level; BEHL, Better ear hearing level; WEHL, Worse ear hearing level; CI, Confidence interval.
|
|
| 14. |
- Lohi, Venla, et al.
(author)
-
Prevalence and incidence of hearing impairment among adults : a 13-year follow-up study
- 2021
-
In: International Journal of Audiology. - : Routledge. - 1499-2027 .- 1708-8186. ; 60:9, s. 687-694
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: The aim of this study was to investigate the prevalence and incidence of hearing impairment (HI) in a longitudinal setting among adults.DESIGN: An unscreened, population-based epidemiological 13-year follow-up study. Study sample: 850 randomly sampled 54 to 66-year-old baseline participants, of whom 559 participated in the follow-up study at the age of 68 to 79 years. A questionnaire-based interview, an otological examination and pure-tone audiometry were performed.RESULTS: The overall prevalence of HI was 70.3%, defined by better ear hearing level (BEHL) ≥ 20 dB in the 0.5-4 kHz frequency range. The prevalence was higher among men (78.6%) than among women (63.7%). The overall incidence rate for HI was 45.8 per 1000 person years and the 13-year cumulative incidence was 60.9%. The incidence was higher among men and older participants.CONCLUSION: HI is highly prevalent and incident among older adults in Northern Finland.
|
|
| 15. |
- Lohi, Venla, et al.
(author)
-
The impact of cardiovascular diseases on hearing deterioration : a 13-year follow-up study
- 2022
-
In: International Journal of Audiology. - : Routledge. - 1499-2027 .- 1708-8186. ; 61:10, s. 826-831
-
Journal article (peer-reviewed)abstract
- OBJECTIVE: To study the impact of cardiovascular diseases (CVDs) on hearing deterioration among ageing adults in a longitudinal setting. Furthermore, to describe the pure tone threshold changes at the 0.125-8 kHz frequency range over 13 years.DESIGN: A population-based follow-up study.STUDY SAMPLE: A random sample of 850 adults, of whom 559 participated in the follow-up study. Otological examination, a structured interview, and pure tone audiometry were conducted. Multivariate regression models were used to estimate the effect of CVD (participants had at least one cardiovascular condition) on hearing deterioration of the better ear hearing level (BEHL), defined as a change in the pure-tone average (PTA) of the frequencies 0.5, 1, 2, and 4 kHz and separately at the lower (0.125, 0.25, and 0.5 kHz) and higher (4, 6, and 8 kHz) frequencies.RESULTS: In the multivariable-adjusted analysis, the BEHL change at 13 years was 0.7 dB greater among participants with CVD (p = 0.3). The mean BEHL change during the 13-year follow-up was 12.0 dB (95% CI 11.4-12.6) among all participants.CONCLUSIONS: No significant association between CVD and hearing threshold changes was found.
|
|
| 16. |
|
|
| 17. |
- Mäki-Torkko, Elina, 1961-, et al.
(author)
-
Hearing impairment among adults : extent of the problem and scientific evidence on the outcome of hearing aid rehabilitation
- 2001
-
In: Scandinavian audiology. Supplementum. - : Taylor & Francis. - 0107-8593 .- 0105-0397. ; 30:54
-
Journal article (peer-reviewed)abstract
- Scientific surveys on current and estimated prevalence of hearing impairment (HI) in adult populations (> or = 18 years of age) in Denmark, Finland, Norway, Sweden and the United Kingdom, and scientific reports on the outcome of hearing aid (HA) rehabilitation worldwide were reviewed. Only a few of the studies meet strict scientific criteria, and many locally clinically relevant studies cannot be generalized to larger populations. Population-based studies indicate an increase in prevalence of HI with age, but because of differences in study populations and available national population statistics, the studies do not allow reliable comparisons between countries or estimation of future prevalence of HI. Studies on HA prescription or outcomes do not provide uniform data in favour of non-linear amplification, but they do show some subject preference for the newer technology. No conclusions can be drawn regarding the degree of HI and the effects of amplification. The literature review alone gives only limited information regarding the extent of the problem of HI in adult populations in the target countries. Similarly, only a few studies on HA outcome meet strict scientific criteria and even fewer studies correlate rehabilitation outcome with the degree of HI, disability or handicap.
|
|
| 18. |
- Mäki-Torkko, Elina, 1961-, et al.
(author)
-
Ikääntyvän kuulo
- 2006
-
In: Suomen lääkärilehti. - 0039-5560. ; 61, s. 1337-1341
-
Journal article (pop. science, debate, etc.)abstract
|
|
| 19. |
- Van Eyken, Els, et al.
(author)
-
Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment
- 2007
-
In: Journal of Medical Genetics. - : B M J Group. - 0022-2593 .- 1468-6244. ; 44:9, s. 570-578
-
Journal article (peer-reviewed)abstract
- BackgroundAge‐related hearing impairment (ARHI) is the most common sensory impairment in older people, affecting 50% of those aged 80 years. The proportion of older people is increasing in the general population, and as a consequence, the number of people affected with ARHI is growing. ARHI is a complex disorder, with both environmental and genetic factors contributing to the disease. The first studies to elucidate these genetic factors were recently performed, resulting in the identification of the first two susceptibility genes for ARHI, NAT2 and KCNQ4.MethodsIn the present study, the association between ARHI and polymorphisms in genes that contribute to the defence against reactive oxygen species, including GSTT1, GSTM1 and NAT2, was tested. Samples originated from seven different countries and were combined into two test population samples, the general European population and the Finnish population. Two distinct phenotypes for ARHI were studied, Zlow and Zhigh, representing hearing in the low and high frequencies, respectively. Statistical analysis was performed for single polymorphisms (GSTM1, GSTT1, NAT2*5A, NAT2*6A, and NAT2*7A), haplotypes, and gene–environment and gene–gene interactions.ResultsWe found an association between ARHI and GSTT1 and GSTM1 in the Finnish population sample, and with NAT2*6A in the general European population sample. The latter finding replicates previously published data.ConclusionAs replication is considered the ultimate proof of true associations in the study of complex disorders, this study provides further support for the involvement of NAT2*6A in ARHI.
|
|
| 20. |
- Van Eyken, Els, et al.
(author)
-
The Contribution of GJB2 (Connexin 26) 35delG to Age-Related Hearing Impairment and Noise-Induced Hearing Loss
- 2007
-
In: Otology and Neurotology. - : Lippincott Williams & Wilkins. - 1531-7129 .- 1537-4505. ; 28:7, s. 970-975
-
Journal article (peer-reviewed)abstract
- Hypothesis: The common GJB2 (Connexin 26) 35delG mutation might contribute to the development of age-related hearing impairment (ARHI) and noise-induced hearing loss (NIHL).Background: GJB2, a gene encoding a gap junction protein expressed in the inner ear, has been suggested to be involved in the potassium recycling pathway in the cochlea. GJB2 mutations account for a large number of individuals with nonsyndromic recessive hearing loss, with 35delG being the most frequent mutation in populations of European origin. Other genes involved in potassium homeostasis have been suggested to be associated with ARHI and NIHL, and distortion product otoacoustic emission distortions indicative of hearing loss alterations have been found in 35delG carriers.Method: We genotyped 35delG in two distinct sample sets: an ARHI sample set, composed of 2,311 Caucasian samples from nine different centers originating from seven different countries with an age range between 53 and 67 years, and an NIHL sample set consisting of 702 samples from the two extremes of a noise-exposed Polish sample.Results: After statistical analysis, we were unable to detect an association between 35delG and ARHI, nor between 35delG and NIHL.Conclusion: Our findings indicate that there is no increased susceptibility in 35delG carriers for the development of ARHI or NIHL.
|
|
| 21. |
- Van Laer, Lut, et al.
(author)
-
A genome-wide association study for age-related hearing impairment in the Saami
- 2010
-
In: European Journal of Human Genetics. - : BMJ Publishing Group Ltd. - 1018-4813 .- 1476-5438. ; 18:6, s. 685-693
-
Journal article (peer-reviewed)abstract
- This study aimed at contributing to the elucidation of the genetic basis of age-related hearing impairment (ARHI), a common multifactorial disease with an important genetic contribution as demonstrated by heritability studies. We conducted a genome-wide association study (GWAS) in the Finnish Saami, a small, ancient, genetically isolated population without evidence of demographic expansion. The choice of this study population was motivated by its anticipated higher extent of LD, potentially offering a substantial power advantage for association mapping. DNA samples and audiometric measurements were collected from 352 Finnish Saami individuals, aged between 50 and 75 years. To reduce the burden of multiple testing, we applied principal component (PC) analysis to the multivariate audiometric phenotype. The first three PCs captured 80% of the variation in hearing thresholds, while maintaining biologically important audiometric features. All subjects were genotyped with the Affymetrix 100 K chip. To account for multiple levels of relatedness among subjects, as well as for population stratification, association testing was performed using a mixed model. We summarised the top-ranking association signals for the three traits under study. The top-ranked SNP, rs457717 (P-value 3.55 x 10(-7)), was associated with PC3 and was localised in an intron of the IQ motif-containing GTPase-activating-like protein (IQGAP2). Intriguingly, the SNP rs161927 (P-value 0.000149), seventh-ranked for PC1, was positioned immediately downstream from the metabotropic glutamate receptor-7 gene (GRM7). As a previous GWAS of a European and Finnish sample set already suggested a role for GRM7 in ARHI, this study provides further evidence for the involvement of this gene.
|
|
| 22. |
- Van Laer, Lut, et al.
(author)
-
The grainyhead like 2 gene (GRHL2), alias TFCP2L3, is associated with age-related hearing impairment
- 2008
-
In: Human Molecular Genetics. - : Oxford University Press. - 0964-6906 .- 1460-2083. ; 17:2, s. 159-169
-
Journal article (peer-reviewed)abstract
- Age-related hearing impairment (ARHI) is the most prevalent sensory impairment in the elderly. ARHI is a complex disease caused by an interaction between environmental and genetic factors. The contribution of various environmental factors has been relatively extensively studied. In contrast, investigations to identify the genetic risk factors have only recently been initiated. In this paper we describe the results of an association study performed on 2418 ARHI samples derived from nine centers from seven European countries. In 70 candidate genes, a total of 768 tag single nucleotide polymorphisms (SNPs) were selected based on HAPMAP data. These genes were chosen among the monogenic hearing loss genes identified in mice and men in addition to several strong functional candidates. After genotyping and data polishing, statistical analysis of all samples combined resulted in a P-value that survived correction for multiple testing for one SNP in the GRHL2 gene. Other SNPs in this gene were also associated, albeit to a lesser degree. Subsequently, an analysis of the most significant GRHL2 SNP was performed separately for each center. The direction of the association was identical in all nine centers. Two centers showed significant associations and a third center showed a trend towards significance. Subsequent fine mapping of this locus demonstrated that the majority of the associated SNPs reside in intron 1. We hypothesize that the causative variant may change the expression levels of a GRHL2 isoform.
|
|
