人类年龄相关性听力损失的全基因组关联和分子联合研究。
A combined genome-wide association and molecular study of age-related hearing loss in H. sapiens.
机构信息
Department of Surgical Sciences, Section of Otorhinolaryngology and Head & Neck Surgery, Uppsala University, SE-751 85, Uppsala, Sweden.
Department of Immunology, Genetics and Pathology, Science for Life Laboratory, Uppsala University, Uppsala, Sweden.
出版信息
BMC Med. 2021 Dec 1;19(1):302. doi: 10.1186/s12916-021-02169-0.
BACKGROUND
Sensorineural hearing loss is one of the most common sensory deficiencies. However, the molecular contribution to age-related hearing loss is not fully elucidated.
METHODS
We performed genome-wide association studies (GWAS) for hearing loss-related traits in the UK Biobank (N = 362,396) and selected a high confidence set of ten hearing-associated gene products for staining in human cochlear samples: EYA4, LMX1A, PTK2/FAK, UBE3B, MMP2, SYNJ2, GRM5, TRIOBP, LMO-7, and NOX4.
RESULTS
All proteins were found to be expressed in human cochlear structures. Our findings illustrate cochlear structures that mediate mechano-electric transduction of auditory stimuli, neuronal conductance, and neuronal plasticity to be involved in age-related hearing loss.
CONCLUSIONS
Our results suggest common genetic variation to influence structural resilience to damage as well as cochlear recovery after trauma, which protect against accumulated damage to cochlear structures and the development of hearing loss over time.
背景
感音神经性听力损失是最常见的感觉缺陷之一。然而，与年龄相关的听力损失的分子贡献尚不完全清楚。
方法
我们在英国生物库（N=362396）中进行了与听力损失相关特征的全基因组关联研究（GWAS），并选择了十个与听力相关的基因产物作为人耳蜗样本染色的高可信度集：EYA4、LMX1A、PTK2/FAK、UBE3B、MMP2、SYNJ2、GRM5、TRIOBP、LMO-7 和 NOX4。
结果
所有蛋白质均在人耳蜗结构中表达。我们的研究结果表明，介导听觉刺激的机电转导、神经元传导和神经元可塑性的耳蜗结构与年龄相关性听力损失有关。
结论
我们的研究结果表明，常见的遗传变异会影响结构对损伤的弹性以及创伤后的耳蜗恢复，从而防止耳蜗结构的累积损伤以及随着时间的推移听力损失的发展。
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