Wang Jun, Liu Dan, Tian E, Guo Zhao-Qi, Chen Jing-Yu, Kong Wei-Jia, Zhang Su-Lin
Department of Otorhinolaryngology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Union Hospital, Institute of Otorhinolaryngology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Front Neurol. 2022 Apr 25;13:876165. doi: 10.3389/fneur.2022.876165. eCollection 2022.
Observational studies have suggested that hearing impairment (HI) was associated with the risk of falls, but it remains unclear if this association is of causal nature.
A two-sample Mendelian randomization (MR) study was conducted to investigate the causal association between HI and falls in individuals of European descent. Summary data on the association of single nucleotide polymorphisms (SNPs) with HI were obtained from the hitherto largest genome-wide association study (GWAS) ( = 323,978), and statistics on the association of SNPs with falls were extracted from another recently published GWAS ( = 461,725). MR Steiger filtering method was applied to determine the causal direction between HI and falls. Inverse-variance weighted (IVW) method was employed as the main approach to analyze the causal association between HI and falls, whereas weighted median, simple mode, weighted mode, and MR-Egger methods were used as complementary analyses. The MR-Egger intercept test, the MR-PRESSO test, and Cochran's Q statistic were performed to detect the potential directional pleiotropy and heterogeneity, respectively. The odds ratio (OR) with 95% confidence intervals (CIs) was used to evaluate this association.
A total of 18 SNPs were identified as valid instrumental variables in our two-sample MR analysis. The positive causality between HI and risk of falls was indicated by IVW [OR 1.108 (95% CI 1.028, 1.194), = 0.007]. The sensitivity analyses yielded comparable results. The "leave-one-out" analysis proved that lack of a single SNP did not affect the robustness of our results. The MR-Egger intercept test exhibited that genetic pleiotropy did not bias the results [intercept = -2.4E-04, SE = 0.001, = 0.832]. Cochran's Q test revealed no heterogeneity.
Our MR study revealed a causal association between genetically predicted HI and falls. These results provide further evidence supporting the need to effectively manage HI to minimize fall risks and improve quality of life.
观察性研究表明，听力障碍（HI）与跌倒风险相关，但这种关联是否具有因果关系仍不清楚。
进行了一项两样本孟德尔随机化（MR）研究，以调查欧洲血统个体中HI与跌倒之间的因果关联。单核苷酸多态性（SNP）与HI关联的汇总数据来自迄今为止最大的全基因组关联研究（GWAS）（n = 323,978），SNP与跌倒关联的统计数据则从另一项最近发表的GWAS（n = 461,725）中提取。采用MR Steiger过滤方法来确定HI与跌倒之间的因果方向。采用逆方差加权（IVW）方法作为分析HI与跌倒之间因果关联的主要方法，而加权中位数、简单模式、加权模式和MR-Egger方法则用作补充分析。分别进行MR-Egger截距检验、MR-PRESSO检验和Cochran's Q统计量以检测潜在的方向性多效性和异质性。使用具有95%置信区间（CI）的比值比（OR）来评估这种关联。
在我们的两样本MR分析中，共鉴定出18个SNP作为有效的工具变量。IVW表明HI与跌倒风险之间存在正向因果关系[OR 1.108（95%CI 1.028，1.194），P = 0.007]。敏感性分析得出了可比的结果。“留一法”分析证明，缺少单个SNP并不影响我们结果的稳健性。MR-Egger截距检验表明基因多效性并未使结果产生偏差[截距 = -2.4E-04，SE = 0.001，P = 0.832]。Cochran's Q检验未显示异质性。
我们的MR研究揭示了基因预测的HI与跌倒之间的因果关联。这些结果提供了进一步的证据，支持需要有效管理HI以将跌倒风险降至最低并改善生活质量。
