Samuli Hannula

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

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 as well as in the low frequencies. The results suggest that a healthy lifestyle can protect against age-related hearing impairment.

Contribution of the N-acetyltransferase 2 polymorphism NAT2*6A to age-related hearing impairment

Background: Age-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. Methods: In 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. Results: We 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. Conclusion: As 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.

A genome-wide association study for age-related hearing impairment in the Saami

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 × 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.

Genome-wide SNP-based linkage scan identifies a locus on 8q24 for an age-related hearing impairment trait.

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.

Self-Reported Hearing Problems among Older Adults: Prevalence and Comparison to Measured Hearing Impairment

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. PURPOSE 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. RESEARCH DESIGN Cross-sectional, population-based, and unscreened. STUDY SAMPLE Random sample of subjects (n=850) aged 54-66 yr living in the city of Oulu (Finland) and the surrounding areas. DATA COLLECTION AND ANALYSIS Otological examination, pure tone audiometry, questionnaire survey RESULTS 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<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. CONCLUSIONS 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.

A genome-wide analysis of population structure in the Finnish Saami with implications for genetic association studies

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 FST 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, FST was smallest for the comparison with the Russians (FST=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.

Hearing in a 54-to 66-year-old population in northern Finland

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 ≥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 (PTA0.5–4 kHz), but a significant difference of −0.8 dB HL was found for the low frequencies 0.125, 0.25, and 0.5 kHz (PTA0.125–0.5 kHz), and 4.4 dB HL for the high frequencies over 4, 6, and 8 kHz (PTA4–8 kHz). In conclusion, HI was a highly prevalent finding in this age group. Sumario Existen pocos estudios epidemiológicos grandes, basados en la población, sobre impedimentos auditivos (HI) en adultos. El objetivo de este estudio fue investigar la prevalencia de HI y posibles diferencias entre los oídos de adultos mayores. La muestra de sujetos (n = 850), con edades de 54–66 años, se hizo al azar, a partir de registros de población. Se aplicó un cuestionario y se realizó un examen otológico y una audiometría de tonos puros. Otro cuestionario fue enviado por correo para colectar información de los no participantes. La prevalencia de HI promediada en las frecuencias de 0.5, 1, 2, y 4 kHz en el mejor oído, >20 dB HL, fue de 26.7% (hombres: 36.8%; mujeres: 18.4%). No hubo diferencia entre los promedios con tonos puros en oídos derecho o izquierdo en las frecuencias de 0.5, 1, 2, y 4 kHz (PTA 0.5–4 kHz), pero si una diferencia significativa de -0.8 dB HL, encontrada en las frecuencias graves de 0.125, 0.25 y 0.5 kHz (PTA 0.125–0.5 kHz), y 4.4 dB HL en las frecuencias agudas de 4, 6 y 8 kHz (PTA 4–8 kHz). En conclusión, el HI fue un hallazgo altamente prevalente en este grupo de edad.

Ear diseases and other risk factors for hearing impairment among adults: An epidemiological study

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 Ménières 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.

Audiogram configurations among older adults: Prevalence and relation to self-reported hearing problems

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 (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: 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. Sumario Objetivo: Existen pocos estudios epidemiológicos poblacionales sobre la configuración de los audiogramas en adultos. El objetivo de este estudio fue investigar la prevalencia de diferentes configuraciones audiométricas entre los adultos mayores. Además se examinaron las configuraciones audiométricas de los sujetos que reportaban problemas auditivos. Diseño: Estudio epidemiológico transversal basado en población no tamizada entre adultos mayores. Muestra: Los sujetos (n = 850), con edades entre 54 y 66 años fueron escogidos al azar de un registro poblacional. Se les aplicó un cuestionario y se realizó un examen otológico y una audiometría tonal. Resultados: la configuración audiométrica más prevalente en hombres fue la de caída abrupta en frecuencias agudas (65.3% oído izquierdo, 51.2% oído derecho) y entre las mujeres fue la caída suave en frecuencias agudas (33% oído izquierdo y 31.5% oído derecho). La configuración plana fue significativamente más frecuente en mujeres que en hombres. Los audiogramas no clasificados fueron comunes, especialmente entre las mujeres (17.5%). Los sujetos que reportaban dificultades auditivas, dificultad para seguir una conversación en ruido o acúfeno presentaban con mayor frecuencia una caída abrupta en frecuencias agudas que aquellos que no lo reportaban. Conclusiones: Las configuraciones audiométricas con caída abrupta en frecuencias agudas fueron más comunes entre quienes reportaron problemas auditivos.

Genome-wide SNP analysis reveals no gain in power for association studies of common variants in the Finnish Saami

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.