Bidirectional Mendelian Randomization Analysis of Genetic Proxies of Plasma Fatty Acids and Pre-Eclampsia Risk

Year: 2024

Type: article

Abstract: Background: Previous studies have reported associations between fatty acids and the risk of pre-eclampsia. However, the causality of these associations remains uncertain. This study postulates a causal relationship between specific plasma fatty acids and pre-eclampsia or other maternal hypertensive disorders (PE-HTPs). To test this hypothesis, two-sample bidirectional Mendelian randomization (MR) analyses were employed to determine the causality effects. Methods: Single-nucleotide polymorphisms associated with PE-HTPs and fatty acids were obtained from a genome-wide association study (GWAS) of European ancestry. Bidirectional MR analyses were conducted using methods such as inverse variance weighted, MR-Egger, weighted median, simple mode, and weighted mode. Sensitivity analyses, including tests for heterogeneity, horizontal pleiotropy, and co-localization, were conducted to assess the robustness of MR results. Results: The analyses revealed causal relationships between PE-HTPs and several fatty acids, including monounsaturated fatty acid (MUFA), omega-6 fatty acid (n-6 FA), linoleic acid (LA), docosahexaenoic acid (DHA), and the PUFA/MUFA ratio. Genetically predicted higher risk of PE-HTPs was significantly associated with lower plasma n-6 FA (OR = 0.96, 95% CI: 0.93–0.99), particularly LA (OR = 0.95, 95% CI: 0.92–0.98). Conversely, increased DHA (OR = 0.86, 95% CI: 0.78–0.96) and a higher PUFA/MUFA ratio (OR = 0.86, 95% CI: 0.76–0.98) were associated with a reduced risk of PE-HTPs. Elevated MUFA levels (OR = 1.12, 95% CI: 1.00–1.25) were related to an increased risk. Conclusions: This study provides robust genetic evidence supporting bidirectional causal relationships between PE-HTPs and specific plasma fatty acids, underscoring the critical role of fatty acid metabolism in maternal hypertensive disorders.

Source: Nutrients

DOI: 10.3390/nu16213748

Authors: Jingqi Zhou, Shuo Jiang, Dangyun Liu, Xinyi Li, Ziyi Zhou, Zhiheng Wang, Hui Wang

Institutions: Shanghai Jiao Tong University, Huaian First People’s Hospital, Nanjing Medical University, Shanghai Medical College of Fudan University, Obstetrics and Gynecology Hospital of Fudan University

Language: English

Topic: Pregnancy and preeclampsia studies

Subfield: Obstetrics and Gynecology

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,296

Funders: Innovative Research Team of High-level Local University in Shanghai, National Natural Science Foundation of China, Science and Technology Commission of Shanghai Municipality, Shanghai Jiao Tong University, National Key Research and Development Program of China, National Human Genome Research Institute

OpenAlex ID: W4403938949