The collection of subjects was a collaborative effort of nine expert audiological centers from seven European countries: two from Belgium (Antwerp, Ghent), two from Finland (Tampere, Oulu), one from The Netherlands (Nijmegen), one from Germany (Tübingen), one from Denmark (Copenhagen), one from Italy (Padua), and one from the UK (Cardiff). To collect study subjects, the audiological centers used three different recruitment strategies: (1) A clinic-based sample, whereby subjects are collected through the regular influx of patients visiting an audiological or ENT clinic. As this strategy tends to recruit an excess of people with poor hearing, the spouses of the recruited subjects were asked to join the study. (2) A population-based sample, whereby subjects were collected via advertisements in local media or through local population registers and letters of invitation. (3) A mixed strategy, whereby part of the samples was population-based and the remaining part was clinic-based. The nine sample sets collected by the audiological centers are hereafter referred to as subsamples.
To make each subpopulation ethnically homogeneous, we requested that at least three out of the four grandparents originated from the same region as the study subject. An effort was made to collect an approximately equal number of males and females and to have a uniform age distribution. All responding subjects underwent clinical examination and otoscopy and completed a detailed questionnaire on medical history and exposure to environmental risk factors. The complete questionnaire is available upon request. A list of all questions and answers used in this paper is provided in Supplementary Table 4. Subjects with ear diseases, possible monogenic forms of hearing impairment, or other major pathologies with a possible influence on hearing were excluded. The main goal was to study hearing impairment in healthy subjects and, therefore, persons with multiple hospitalizations were excluded. The complete list of exclusion criteria was previously reported (Van Eyken et al. 2006 (link)). In subjects passing the medical exclusion criteria, audiometric thresholds were determined for air conduction (0.25, 0.5, 1, 2, 3, 4, 6, and 8 kHz) and bone conduction (0.5, 1, 2, and 4 kHz) according to current clinical standards (ISO 8253). We excluded subjects with asymmetrical hearing loss (between-ear difference in air conduction threshold larger than 20 dB for at least two frequencies out of 0.5, 1, and 2 kHz). In case only one of the ears showed conductive hearing loss (air–bone gap of 15 dB or more at 0.5, 1, and 2 kHz) and in the absence of other exclusion criteria, the other ear could be included.
Research was approved by the ethical committees of the institutions connected to each research center: University of Antwerp, University Hospital of Antwerp, University of Oulu, University Medical Center Nijmegen, Bispebjerg Hospital Copenhagen, University of Tübingen, University Hospital Padova, Cardiff University, University Hospital of Ghent, University of Tampere, and University of Bonn. All persons gave their informed consent before inclusion in this study.