RESUMEN
Background: According to observational research, migraine may increase the risk of Meniere's disease (MD). The two have not, however, been proven to be causally related. Methods: Using Mendelian random (MR) analysis, we aimed to evaluate any potential causal relationship between migraine and MD. We extracted single-nucleotide polymorphisms (SNPs) from large-scale genome-wide association studies (GWAS) involving European individuals, focusing on migraine and MD. The main technique used to evaluate effect estimates was inverse-variance weighting (IVW). To assess heterogeneity and pleiotropy, sensitivity analyses were carried out using weighted median, MR-Egger, simple mode, weighted mode, and MR-PRESSO. Results: There was no discernible causative link between genetic vulnerability to MD and migraine. The migraine dose not increase the prevalence of MD in the random-effects IVW method (OR = 0.551, P = 0.825). The extra weighted median analysis (OR = 0.674, P = 0.909), MR-Egger (OR = 0.068, P = 0.806), Simple mode (OR = 0.170, P = 0.737), and Weighted mode (OR = 0.219, P= 0.760) all showed largely consistent results. The MD dose not increase the prevalence of migraine in the random-effects IVW method (OR = 0.999, P = 0.020). The extra weighted median analysis (OR = 0.999, P = 0.909), MR-Egger (OR = 0.999, P = 0.806), Simple mode (OR = 0.999, P = 0.737), and Weighted mode (OR = 1.000, P = 0.760). Conclusion and significance: This Mendelian randomization study provides casual evidence that migraine is not a risk factor for MD and MD is also not a risk factor for migraine.
RESUMEN
Introduction: myo7aa, the homolog of the human Usher 1B syndrome pathogenic gene, myo7A, plays an important role in stereociliary development and maintenance, therefore, is critical for hearing and balance. However, the molecular mechanisms that myo7aa regulate hearing and balance still need to be studied. Methods: In this study, we generated two independent zebrafish myo7aa knockout lines using CRISPR/Cas9 technology. To investigate the effects of myo7aa on hearing, YO-PRO-1 staining and startle response assay were used. To gain insight into the specific molecular mechanisms by which myo7aa affects hearing, transcriptome sequencing and bioinformatics analysis were employed. Results: Our study showed that hair cells of myo7aa-/- zebrafish can not take up YO-PRO-1 fluorescent dye and are insensitive to acoustic stimulation in myo7aa-/- zebrafish compared to wild type. Genes related to the Rho GTPase signaling pathway, such as arhgap33, dab2ip, and arghef40, are significantly down-regulated in myo7aa-/- zebrafish embryos at 3 dpf. GTP and ATP compensation can partially rescue the hair cell defects in myo7aa knockout zebrafish. Discussion: Our findings suggest that zebrafish myo7aa affects congenital hearing by regulating Rho GTPase signaling, and loss of myo7aa leads to abnormal Rho GTPase signaling and impairs hair cell function. myo7aa, myo7A, arhgap33, dab2ip, arghef40 and myo7aa-/- fonts in the abstract are italicized. -/- is a superscript format.