Exploring the Impact of Neuroticism on Lung Cancer Risk: Insights From Mediated Mendelian Randomization

Abstract

Objective

This study aimed to explore the potential association between neuroticism and lung cancer.

Methods

We conducted analyses on publicly accessible aggregated data from genome-wide association studies (GWAS) that included individuals of European descent. The objective was to identify single nucleotide polymorphisms (SNPs) significantly associated with neuroticism and utilize them as instrumental variables in a two-sample Mendelian randomization framework to evaluate the gender-specific causal link between neuroticism and lung cancer risk.

We applied four statistical methods: Inverse variance weighting (IVW), weighted median, MR-Egger regression, and weighted mode. Our analysis also considered the mediating effect of educational attainment on this relationship.

Results

We selected 67 SNPs associated with neuroticism at genome-wide significance levels from GWAS datasets. Our primary findings using IVW suggest a notable increase in lung cancer risk associated with neuroticism across the general population (odds ratio [OR] = 1.175; 95% confidence interval [CI] 1.020–1.354, p = 0.026). Gender-specific analysis revealed that neuroticism posed a slight but significant risk increase in men (OR = 1.006; 95% CI 1.000–1.012, p = 0.045) and women (OR = 1.005; 95% CI 1.002–1.009, p = 0.002), with findings corroborated by the additional statistical methods. Further, evidence from both observational and Mendelian randomization analyses suggests that genetically predicted neuroticism is causally associated with a modestly increased risk of incident lung cancer, with ∼17% of this effect mediated by educational attainment.

Conclusions

The results from this Mendelian randomization study provide robust evidence supporting a potential association between neuroticism and an increased risk of lung cancer. This association appears more pronounced in men than women. Additionally, educational level serves as a mediator in the nexus between these conditions, suggesting that interventions aimed at increasing educational attainment might mitigate some of the risk neuroticism poses for developing lung cancer.