Objective: In recent years, several studies have reported an association between unsaturated fatty acids (UFAs) and the risk of developing preeclampsia; however, its exact causal effect is unclear. This study assessed the causal association between circulating UFAs and preeclampsia.
Methods: A two-sample Mendelian randomization (MR) study using publicly available genome-wide association study (GWAS) summary data for circulating UFA s (N = 114,999) and preeclampsia (N = 118,291) was performed. Single nucleotide polymorphisms (SNPs) significantly associated with exposure was selected as instrumental variables (IVs). The inverse variance weighted (IVW) test was used as the primary method for estimating causality in MR analysis, while MR pleiotropy residual sum and outlier (MR-PRESSO) and MR-Egger regression methods were used to assess horizontal pleiotropy. Cochran's Q test was used to evaluate heterogeneity among SNPs, and leave-one-out sensitivity analysis was used to determine the effect of individual SNPs on the results of the MR analysis. Bonferroni correction was used as a correction for multiple corrections.
Results: Two-sample MR analysis suggested that the ratio of monounsaturated fatty acids (MUFAs) to total fatty acids (OR 1.150, 95% CI 1.006-1.315, p = 0.041), the ratio of polyunsaturated fatty acids (PUFAs) to total fatty acids (OR 0.805, 95% CI 0.658-0.986, p = 0.036) and the ratio of PUFAs to MUFAs (OR 0.807, 95% CI 0.694-0.938, p = 0.005) were causally associated with preeclampsia. After Bonferroni correction, the causal association between the ratio of polyunsaturated to MUFAs and preeclampsia remained statistically different.
Conclusions: This MR analysis provides evidence for a genetic causal association between circulating UFAs and preeclampsia.
Keywords: Mendelian randomization; Pregnancy; causality; preeclampsia; unsaturated fatty acid.