The importance of accurate phenotyping in large-scale analyses of common disorders such as hearing loss.

Abstract

Age-related hearing loss (ARHL) is a common, complex disease with high heritability, but its underlying genetic landscape remains unclear. Studying such a condition requires large cohorts, detailed genotyping, and deep phenotyping. However, while large cohorts with next-generation sequence data are becoming increasingly common, the challenge of administering audiometric tests at scale has meant that in-depth auditory phenotyping is rarely included. Here we present our analyses of three cohorts with different forms of phenotype data, which reveal the differences made by even small changes in phenotyping. Detailed audiometry enables interrogation of genetic data by auditory phenotypes, but if these data are not available, self-reports of hearing difficulty may also serve. However, relying on medical records alone is ineffective for classifying biobank participants for a common condition like ARHL, and is likely to result in many people being wrongly classified in the control group.