Investigating causal relationships between extensive peripheral immune cell phenotypes and preeclampsia: A bi-directional Mendelian randomization analysis

Chung-Chih Liao; Ju-Chun Ku; Cheng-Li Lin; Ju-Wan Li; Fuu-Jen Tsai; Jung-Miao Li

doi:10.1111/aji.13840

Investigating causal relationships between extensive peripheral immune cell phenotypes and preeclampsia: A bi-directional Mendelian randomization analysis

Am J Reprod Immunol. 2024 Apr;91(4):e13840. doi: 10.1111/aji.13840.

Authors

Chung-Chih Liao^{1

2}, Ju-Chun Ku³, Cheng-Li Lin⁴, Ju-Wan Li⁵, Fuu-Jen Tsai^{3

6

7

8}, Jung-Miao Li^{3

9}

Affiliations

¹ Department of Post-Baccalaureate Veterinary Medicine, College of Medical and Health Science, Asia University, Taichung, Taiwan.
² Chuyuan Chinese Medicine Clinic, Taichung, Taiwan.
³ School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan.
⁴ Management Office for Health Data, China Medical University Hospital, Taichung, Taiwan.
⁵ Anxin Postpartum Nursing Home, Lee Women's Hospital, Taichung, Taiwan.
⁶ Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
⁷ Division of Medical Genetics, China Medical University Children's Hospital, Taichung, Taiwan.
⁸ Department of Biotechnology and Bioinformatics, Asia University, Taichung, Taiwan.
⁹ Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan.

PMID: 38606695
DOI: 10.1111/aji.13840

Abstract

Problem: Preeclampsia, a multifaceted condition during pregnancy characterized by hypertension and organ dysfunction, poses significant risks to both maternal and fetal health. This study aims to investigate the bidirectional causal relationship between peripheral immune cell phenotypes and preeclampsia using a two-sample Mendelian randomization (MR) approach.

Method of study: Genetic data from two sizable cohorts were utilized: 3757 individuals from Sardinia, providing information on 731 immune traits, and 200 929 Finnish adult females, encompassing 6663 preeclampsia cases. Single-nucleotide polymorphisms served as instrumental variables. The MR analyses employed the inverse variance-weighted (IVW) method as the primary tool, supplemented by MR-Egger, weighted median, and weighted mode methods to enhance reliability and address potential heterogeneity and horizontal pleiotropy.

Results: Among the 731 immune cell phenotypes studied, 18 displayed a suggestive positive association (IVW p < .05) with heightened preeclampsia risk, while 20 exhibited a suggestive negative association linked to reduced risk. Following false discovery rate (FDR) adjustment, four immune phenotypes showed significant associations with decreased preeclampsia risk: CD27 on CD24+ CD27+ B cells (B-cell panel) (odds ratio [OR] = 0.927, P_FDR= 0.061), CD33+ HLA DR+ CD14- absolute count (OR = 0.963, P_FDR= 0.061), CD80 on plasmacytoid dendritic cells (OR = 0.923, P_FDR= 0.061); and CD80 on CD62L+ plasmacytoid dendritic cells (OR = 0.923, P_FDR= 0.061). In the reverse-direction MR analysis, no significant causal effects of preeclampsia on immune cell phenotypes were observed.

Conclusions: This study provides quantifiable evidence linking specific immune cell phenotypes to the risk of developing preeclampsia. This novel understanding of the immunological aspects underlying preeclampsia's pathogenesis could lead to innovative therapeutic strategies centered on immune modulation.

Keywords: causal relationships; immune cell phenotypes; mendelian randomization; preeclampsia; single‐nucleotide polymorphisms.

MeSH terms

Adult
Female
Humans
Hypertension*
Mendelian Randomization Analysis
Phenotype
Pre-Eclampsia* / genetics
Pregnancy
Reproducibility of Results