Association Between Unsaturated Fatty Acid Levels and Chronic Obstructive Pulmonary Disease: A Bidirectional Mendelian Randomization Study

Abstract

Background: Observational studies have revealed that the levels of unsaturated fatty acids (UFAs) may influence the development, progression, and management of chronic obstructive pulmonary disease (COPD). To investigate the association between UFAs and COPD, we performed a bidirectional Mendelian randomization (MR) study.

Methods: We extracted summary genome-wide association statistics (GWAS) for UFAs (N = 115 082) among population from UK Biobank study by measuring circulating lipoprotein lipid concentrations. The genetic instrument for COPD was derived from the FinnGen, which included 338 303 COPD controls and 20 066 cases of the disease. Measured at the genome-wide significance level, independent genetic variations associated with each characteristic were considered instrumental factors. Two-sample MR analysis was mainly conducted utilizing the inverse-variance-weighted (IVW) approach, complemented by the weighted median method and the MR-Egger regression.

Results: IVW MR analysis significantly demonstrated that the level of docosahexaenoic acid (DHA) (OR 0.812, 95% CI 0.719-0.918, p < 0.001), linoleic acid (LA) (OR 0.850, 95% CI 0.781-0.926, p < 0.001), the levels of omega-3 fatty acids (OR 0.884, 95% CI 0.781-0.99, p = 0.049), omega-6 fatty acids (OR 0.878, 95% CI 0.812-0.950, p = 0.001), and polyunsaturated fatty acids (PUFAs) (OR 0.901, 95% CI 0.827-0.982, p = 0.018) all linked to a higher risk of COPD. Moreover, in reverse direction MR analysis, genetic liability to COPD showed associations with higher levels of monounsaturated fatty acids (MUFAs) (OR 1.040, 95% CI 1.010-1.071, p = 0.008). Horizontal pleiotropy is not likely to materially skew the causative estimates from sensitivity analysis.

Conclusion: Our research added credence to the current evidence that suggests a bidirectional causal link between UFAs and COPD. It is imperative to comprehend this connection in order to effectively prevent and manage COPD.

Keywords: Mendelian randomization (MR); chronic obstructive pulmonary disease (COPD); risk factors; unsaturated fatty acids (UFAs).