Circulating adipokine levels and preeclampsia: A bidirectional Mendelian randomization study

Xiaoyan Chen; Zhaoming Liu; Jingen Cui; Xiaolan Chen; Jing Xiong; Wei Zhou

doi:10.3389/fgene.2022.935757

Circulating adipokine levels and preeclampsia: A bidirectional Mendelian randomization study

Front Genet. 2022 Aug 22:13:935757. doi: 10.3389/fgene.2022.935757. eCollection 2022.

Authors

Xiaoyan Chen¹, Zhaoming Liu¹, Jingen Cui¹, Xiaolan Chen¹, Jing Xiong¹, Wei Zhou¹

Affiliation

¹ Department of Obstetrics, Chongqing Health Center for Women and Children, Women and Children's Hospital of Chongqing Medical University, Chongqing, China.

Abstract

Background: Several observational studies have demonstrated that significantly rising circulating adipokine levels are pervasive in preeclampsia or eclampsia disorder (or preeclampsia toxemia (PET)). However, it remains unclear whether this relationship is causal. In this study, we sought to elucidate the causal effects of circulating adipokine levels on PET. Methods: Summary-level data and independent genetic variants strongly associated with common adipokine molecule (adiponectin, leptin, resistin, sOB-R, and PAI-1) levels were drawn from public genome-wide association study (GWASs). Additionally, the corresponding effects between instrumental variables and PET outcomes were acquired from the FinnGen consortium, including 4,743 cases and 136,325 controls of European ancestry. Subsequently, an inverse-variance weighted (IVW) approach was applied for the principal two-sample Mendelian randomization (MR) and multivariable MR (MVMR) analyses. Various complementary sensitivity analyses were then carried out to determine the robustness of our models. Results: The results of the IVW method did not reveal any causal relationship shared across genetically predisposed adipokine levels and PET risk (for adiponectin, OR = 0.86, 95% CI: 0.65-1.13, p = 0.274). Additionally, no significant associations were identified after taking into account five circulating adipokines in MVMR research. Complementary sensitivity analysis also supported no significant associations between them. In the reverse MR analysis, genetically predicted PET risk showed a suggestive association with elevating PAI-1 levels by the IVW method (Beta = 0.120, 95% CI: 0.014, 0.227, p = 0.026). Furthermore, there were no strong correlations between genetic liability to PET and other adipokine levels (p > 0.05). Conclusion: Our MR study did not provide robust evidence supporting the causal role of common circulating adipokine levels in PET, whereas genetically predicted PET may instrumentally affect PAI-1 levels. These findings suggest that PAI-1 may be a useful biomarker for monitoring the diagnosis or therapy of PET rather than a therapeutic target for PET.

Keywords: Mendelian randomization; adipokine; genetic epidemiology; preeclampsia; single nucleotide polymorphism.