Department of Neurology, Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan.
Brain Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Commun Biol. 2024 Aug 22;7(1):1034. doi: 10.1038/s42003-024-06603-w.
The contributing genetic factors of vertigo remain poorly characterized, particularly in individuals of non-European ancestries. Here we show the genetic landscape of vertigo in an Asian population-based cohort. In a two-stage genome-wide association study (N = 6199; N = 54,587), we identify vertigo-associated genomic loci in DROSHA and ZNF91/LINC01224, with the latter replicating the findings in European ancestries. Gene-based association testing corroborates these findings. Interestingly, both genes are enriched in cerebellum, a key structure receiving sensory input from the vestibular system. Subjects carrying risk alleles from lead SNPs of DROSHA and ZNF91 incur a 1.74-fold risk of vertigo than those without. Moreover, composite clinical-polygenic risk scores allow differentiation between patients and controls, yielding an area under receiver operating characteristic curve of 0.69. This study identified novel genomic loci for vertigo in an Asian population-based cohort, which may help identifying high risk subjects and provide mechanistic insight in understanding the pathogenesis of vertigo.
眩晕的致病遗传因素仍未得到充分描述,尤其是在非欧洲血统的个体中。在这里,我们展示了基于亚洲人群的队列中眩晕的遗传特征。在两阶段全基因组关联研究(N=6199;N=54587)中,我们在 DROSHA 和 ZNF91/LINC01224 中确定了与眩晕相关的基因组位点,后者在欧洲血统人群中复制了这些发现。基于基因的关联测试证实了这些发现。有趣的是,这两个基因在小脑中都很丰富,小脑是从前庭系统接收感觉输入的关键结构。与不携带 DROSHA 和 ZNF91 先导 SNP 风险等位基因的受试者相比,携带这些 SNP 风险等位基因的受试者患眩晕的风险增加了 1.74 倍。此外,综合临床多基因风险评分可区分患者和对照组,其受试者工作特征曲线下面积为 0.69。这项研究在基于亚洲人群的队列中确定了眩晕的新的基因组位点,这可能有助于识别高风险人群,并为理解眩晕的发病机制提供机制上的见解。