Mendelian Randomization Analysis of Human Blood Metabolites and Sensorineural Hearing Loss

The role of the human blood metabolites and sensorineural hearing loss (SNHL) has been extensively studied, but the exact causal relationship remains uncertain. To address this knowledge gap, two-sample Mendelian randomization (MR) analysis was employed to investigate the potential causal effects of blood metabolites on the risk of developing SNHL.

Genetic associations with SNHL were mainly derived from FinnGen (cases: 44,745; controls: 437,331), while human blood metabolites were extracted from met-a, met-d, and 1400 blood metabolites. Inverse variance weighted (IVW) and other MR methods, such as MR-Egger, weighted median, simple mode, MR-PRESSO and Steiger Test were used to explore the causal relationship between blood.

In the met-d cohort, a causal association was identified between four lipid metabolites and SNHL. Specifically, free cholesterol-to-total lipids ratio in small very-low-density lipoprotein (VLDL) (IVW OR = 0.95, 95% CI = 0.92-0.99, FDR p = 0.01), free cholesterol-to-total lipids ratio in medium VLDL (IVW OR = 0.93, 95% CI = 0.90-0.97, FDR p = 0.00), and cholesterol-to-total lipids ratio in large high-density lipoprotein (HDL) (IVW OR = 0.94, 95% CI = 0.91-0.98, FDR p = 0.00) were significantly associated with a reduced risk of SNHL. Furthermore, the average diameter of VLDL particles (IVW OR = 1.06, 95% CI = 1.01-1.11, FDR p = 0.01) was significantly associated with an increased risk of SNHL. In contrast, within the met-a cohort and across the 1400 blood metabolites analyzed, no blood metabolites were identified to be associated with SNHL. After conducting the Steiger Test, we did not find any reverse causality.

Our MR Study provides support for the genetic evidence of a causal connection between blood metabolites and SNHL. Additionally, it offers new insights into the exploration of strategies for the prevention and management of SNHL.