Is Hearing Impairment Causally Associated With Falls? Evidence From a Two-Sample Mendelian Randomization Study

Abstract

Background: 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.

Methods: 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) (n = 323,978), and statistics on the association of SNPs with falls were extracted from another recently published GWAS (n = 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.

Results: 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), p = 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, p = 0.832]. Cochran's Q test revealed no heterogeneity.

Conclusion: 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.

Keywords: Mendelian randomization; causal association; falls; genome-wide association study; hearing impairment.

Figure 1

Design of the two-sample Mendelian randomization study. IVs, instrumental variables; HI, hearing impairment; SNP, single nucleotide polymorphism.

Figure 2

Scatter plot of the effects of genetic variants on the HI and falls. The slopes of the solid lines denote the magnitudes of the associations estimated from the MR analyses. HI, hearing impairment; MR, Mendelian randomization; SNP, single-nucleotide polymorphism.

Figure 3

Fixed-effect IVW analysis of the causal association of HI with falls. The black dots and bars indicate the causal estimate and 95% CI using each SNP. The red dot and bar indicate the overall estimate and 95% CI meta-analyzed by fixed-effect IVW method. IVW, inverse-variance weighted; HI, hearing impairment; CI, confidence interval; SNP, single nucleotide polymorphism.

Figure 4

“Leave-one-out” analysis of the causal association of HI with falls. The black dots and bars indicate the causal estimate and 95% CI when an SNP was removed in turn. The red dot and bar indicate the overall estimate and 95% CI using the fixed-effect IVW method. HI, hearing impairment; CI, confidence interval; SNP, single nucleotide polymorphism; IVW, inverse-variance weighted.