Transcriptome-wide association study identifies novel susceptibility genes contributing to hearing impairment 

Abstract

Hearing impairment (HI) is a growing public health issue of global concern, which may lead to decreased work efficiency, social withdrawal and depression. However, the knowledge of the genetic basis of HI is limited. We conducted a transcriptome-wide association study (TWAS) on risk of HI by combining an European cohort (578 cases and 583 controls) with a Chinese cohort (89 cases and 209 controls). We identified that 46 genes show transcriptome-wide significant associations with the HI risk in the meta-analyses of the European and the Chinese cohorts (all P < 3.96 ×10− 6). Of these 46 candidate genes, four genes (ARL6IP6, TMEM127, TOMM7 and JAM3) showed nominal evidence of association in both cohorts (all P < 0.05). Among these four genes, two ones (ARL6IP6 and TMEM127) revealed strong, colocalized, and potentially causal associations with HI. Pathway enrichment analyses showed that the ciliary landscape (P = 5.55 × 10− 4), cholesterol biosynthesis (P = 7.09 × 10− 3), glycerophospholipid metabolism (P = 9.65 × 10− 3) and IL-4 (P = 1.11 × 10− 2) signaling pathways are significantly associated with HI. Our findings identified several novel susceptibility genes contributing to HI, and emphasized the power of TWAS in identifying putatively causal genes for common diseases.

Untargeted metabolomics of the cochleae from two laryngeally echolocating bats

“…It was also identified that metabolites that showed a significant difference in accumulation between microtia and healthy ear cartilage were associated with Pantothenate and CoA biosynthesis, so these may have an association with the development of microtia ear cartilage ( Yang and He, 2020 ). Finally, with regard to Glycerophospholipid metabolism, this has potential protective roles in the cochlea, which was reported to be significantly related to noise-induced hearing loss ( Xie et al, 2021 ). Taken together, our results indicated that different metabolic processes presenting in the cochleae of R. sinicus and V. sinensis .…”

Hippocampal Transcriptome-Wide Association Study Reveals Correlations Between Impaired Glutamatergic Synapse Pathway and Age-Related Hearing Loss in BXD-Recombinant Inbred Mice

“…Transcriptome-wide association study (TWAS) is a powerful tool to investigate the association between gene expression and traits ( Civelek and Lusis, 2014 ; Wainberg et al, 2019 ). Novel susceptibility genes contributing to hearing impairment were identified with this approach ( Xie et al, 2021 ). TWAS relies on the large-scale transcriptomic analysis from a genetic reference population (GRP).…”