A Genome-Wide Association Study of Age-Related Hearing Impairment in Middle- and Old-Aged Chinese Twins

Journal of biomedicine & biotechnology

article

Haiping Duan¹  Dongfeng Zhang¹  Wanxue Song¹  Weijing Wang¹  Hainan Cao⁴  Bingling Wang²  Yan Liu²  Chunsheng Xu²  Yili Wu¹  Zengchang Pang² 

[1] Department of Epidemiology and Health Statistics, Public Health College, Qingdao University;Qingdao Municipal Center for Disease Control and Prevention;Qingdao Institute of Preventive Medicine;Department of Otorhinolaryngology, Qingdao Municipal Hospital

DOI  :  10.1155/2021/3629624

来源: Hindawi Publishing Corporation

【 摘 要 】

Background . Age-related hearing impairment (ARHI) is considered an unpreventable disorder. We aimed to detect specific genetic variants that are potentially related to ARHI via genome-wide association study (GWAS). Methods . A sample of 131 dizygotic twins was genotyped for single-nucleotide polymorphism- (SNP-) based GWAS. Gene-based test was performed using VEGAS2. Pathway enrichment analysis was conducted by PASCAL. Results . The twins are with a median age of 49 years, of which 128 were females and 134 were males. rs6633657 was the only SNP that reached the genome-wide significance level for better ear hearing level (BEHL) at 2.0 kHz ( ). Totally, 9, 10, 42, 7, 17, and 5 SNPs were suggestive evidence level for ( ) BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and pure tone average (PTA), respectively. Several promising genetic regions in chromosomes (near the C20orf196, AQPEP, UBQLN3, OR51B5, OR51I2, OR52D1, GLTP, GIT2, and PARK2) nominally associated with ARHI were identified. Gene-based analysis revealed 165, 173, 77, 178, 170, and 145 genes nominally associated with BEHLs at 0.5, 1.0, 2.0, 4.0, and 8.0 kHz and PTA, respectively ( ). For BEHLs at 0.5, 1.0, and 2.0 kHz, the main enriched pathways were phosphatidylinositol signaling system, regulation of ornithine decarboxylase, eukaryotic translation initiation factor (EIF) pathway, amine compound solute carrier (SLC) transporters, synthesis of phosphoinositides (PIPS) at the plasma membrane, and phosphatidylinositols (PI) metabolism. Conclusions . The genetic variations reported herein are significantly involved in functional genes and regulatory domains that mediate ARHI pathogenesis. These findings provide clues for the further unraveling of the molecular physiology of hearing functions and identifying novel diagnostic biomarkers and therapeutic targets of ARHI.

【 授权许可】

Unknown