Complex Mechanisms of Hearing Loss: Integrating Genomics, Environment, and Phenotypic Diversity

Hearing loss is one of the most prevalent sensory disorders worldwide, associated with social isolation, depression, cognitive decline, and increased risk of dementia. Hearing loss is a multifactorial condition influenced by both genetic predispositions and environmental exposures. While numerous genetic variants have been linked to diverse hearing loss phenotypes, the interplay between these variants and environmental factors - such as noise exposure, psychosocial stressors, ototoxic medications, diet, and lifestyle - remains insufficiently understood. Additionally, hearing loss exhibits marked phenotypic heterogeneity. Diverse variants in genes contribute to a wide spectrum of auditory phenotypes, age at onset, and progression. Mutations in ACTG1 (γ-actin) exemplify this complexity, spanning Baraitser-Winter syndrome type 2 to non-syndromic and late-onset hearing loss, and overlapping mechanistic pathways with genes such as TBC1D24. Similar variability is observed for other recurrently implicated genes, underscoring intricate genotype-phenotype correlations, pleiotropy, and potential gene-gene and gene-environment interactions. Understanding these interactions is essential for precision medicine approaches, risk stratification, and preventive strategies.This Research Topic invites studies that elucidate how genetic susceptibility interacts with environmental influences to shape diverse hearing outcomes. By leveraging advanced genomic sequencing, protein modeling, and experimental model systems, researchers can dissect variant-specific roles, investigate gene-environment interactions, and identify potential diagnostic biomarkers and therapeutic targets.This research topic aims to bridge knowledge gaps, advance precision diagnostics and intervention, and contribute to a broader understanding of the genetic and environmental architecture underlying hearing loss and sensory disorders. Topic editors: Rong Jiang, Katherina Walz Source: https://www.frontiersin.org/research-topics/76393/complex-mechanisms-of-hearing-loss-integrating-genomics-environment-and-phenotypic-diversity