A genome-wide association study about presbycusis and brain cortical structure: Neuroimaging traits from a Mendelian randomization study.

OBJECTIVES

The causal association between presbycusis and changes in cerebral cortex structure was evaluated through Mendelian randomization (MR).

METHODS

Presbycusis data, serving as the exposure trait, was analyzed using data from the ninth release of the FinnGen biobank. Genome-wide association study (GWAS) datasets for cortical surface area (SA) and thickness (TH) were sourced from the ENIGMA Consortium, whereas cortical volume (V) GWAS data came from the UK Biobank. The inverse-variance weighted (IVW) approach was adopted as the principal analytical method. To ensure robustness, sensitivity analyses were systematically implemented to evaluate potential heterogeneity and pleiotropic effects.

RESULTS

Following rigorous filtering through IVW and sensitivity analyses, eleven robust MR associations emerged, offering preliminary evidence for a causal link between presbycusis and cortical architecture, including frontal pole SA with global weighted (GW) (β=1.858 mm2, P=0.004) and without GW (β=1.778 mm2, P=0.012), pars orbitalis SA with GW (β=2.717 mm2, P=0.042), transverse temporal SA with GW (β=2.349 mm2, P=0.033), pars orbitalis TH with GW (β=-0.009 mm, P=0.008) and without GW (β=-0.011 mm, P=0.008), rostral middle frontal TH with GW (β=-0.005 mm, P=0.020) and without GW (β=-0.007 mm, P=0.012), precuneus TH without GW (β=-0.006 mm, P=0.049), left hippocampus V (β=-12.296 mm3, P=0.033) and right hippocampus V (β=-11.991 mm3, P=0.049).

CONCLUSION

From a genetic standpoint, our findings indicate region-specific neuroanatomical modifications in presbycusis patients, supporting the notion of neurodegenerative or adaptive alterations in brain structure from a genetic perspective.