Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss

Genome-wide association meta-analysis identifies five novel loci for age-related hearing impairment

Previous research has shown that genes play a substantial role in determining a person's susceptibility to age-related hearing impairment. The existing studies on this subject have different results, which may be caused by difficulties in determining the phenotype or the limited number of participants involved. Here, we have gathered the largest sample to date (discovery n = 9,675; replication n = 10,963; validation n = 356,141), and examined phenotypes that represented low/mid and high frequency hearing loss on the pure tone audiogram. We identified 7 loci that were either replicated and/or validated, of which 5 loci are novel in hearing. Especially the ILDR1 gene is a high profile candidate, as it contains our top SNP, is a known hearing loss gene, has been linked to age-related hearing impairment before, and in addition is preferentially expressed within hair cells of the inner ear. By verifying all previously published SNPs, we can present a paper that combines all new and existing findings to date, giving a complete overview of the genetic architecture of age-related hearing impairment. This is of importance as age-related hearing impairment is highly prevalent in our ageing society and represents a large socio-economic burden

Diabetes and Auditory-Vestibular Pathology

The relationship between diabetes mellitus (DM) and the auditory/vestibular system has been investigated for more than a century. Most population-based investigations of hearing loss in persons with diabetes (PWD) have revealed a slow progressive, bilateral, high-frequency sensorineural hearing loss. Despite the growing research literature on the pathophysiology of DM-related hearing loss using various animal models and other human studies, knowledge of specific mechanism of the degenerative changes of the inner ear and/or auditory nerve is far from full elucidation. Recent investigations of the mechanisms underlying the association between hearing loss and DM suggest complex combined contributions of hyperglycemia, oxidative stress resulting in cochlear microangiopathy, and auditory neuropathy. An even lesser understood complication of DM is the effect on the vestibular system. Here we provide an overview of animal and human evidence of pathophysiological changes created by DM and its effects on auditory-vestibular anatomy and function