Sleep-Associated Traits and Hearing Difficulties in Noise: A Bidirectional Mendelian Randomization Study.

Objectives: The aim of this study was to investigate the causal relationships between sleep-associated traits and hearing difficulties in noise (HDinN) by Mendelian randomization (MR) analysis.

Design: Single nucleotide polymorphisms associated with chronotype, insomnia, sleep duration, daytime dozing or sleeping, and ease of getting up in the morning were extracted from European population genome-wide association study pooled data for bidirectional MR analysis. The MR-Egger regression, the inverse variance weighted technique, and the weighted median method were used for data analysis. The study was then expanded to include South Asian, East Asian, African, and Greater Middle Eastern populations.

Results: MR analysis indicated that in European populations, ease of getting up in the morning is a protective factor for HDinN (odds ratio [OR] = 0.932, p = 4.22 × 10-5, pFDR = 5.62 × 10-4), while shorter sleep duration was a risk factor (undersleepers: OR = 1.164, p = 0.002, pFDR = 0.014). In addition, there was an indicative causal association between daytime dozing and HDinN (OR = 1.089, p = 0.046, pFDR = 0.123). The conclusions were consistent in African populations (ease of getting up: OR = 0.696, p = 0.012, pFDR = 0.041, sleep duration: OR = 0.677, p = 0.032 pFDR = 0.091, daytime dozing: OR = 1.164, p = 0.002, pFDR = 0.014). In the reverse direction, there was a significant causal association between HDinN and both chronotype (OR = 1.413, p = 0.011, pFDR = 0.042) and ease of getting up in the morning (OR = 0.668, p = 1.75 × 10-5, pFDR = 3.49 × 10-4) in European populations, with similar conclusions respectively reached in East Asian (OR = 1.085, p = 0.010, pFDR = 0.045) and African populations (OR = 0.936, p = 0.002, pFDR = 0.012). Furthermore, although not observed in European populations, exploratory studies in non-European populations suggested a potential association between insomnia and HDinN (East Asian: OR = 1.920, p = 0.011, pFDR = 0.043, African: OR = 2.080, p = 0.004, pFDR = 0.019, South Asian: OR = 1.981, p = 1.59 × 10-4, PFDR = 0.002, Greater Middle Eastern: OR = 2.394, p = 0.002, pFDR = 0.012), and vice versa (Greater Middle Eastern: OR = 1.056, p = 0.014, pFDR = 0.044).

Conclusions: This study identified a potential bidirectional causal relationship between sleep-associated traits and HDinN. However, the underlying mechanisms of the causal relationships reported here have yet to be elucidated.