Genetic association studies in pre-eclampsia: systematic meta-analyses and field synopsis

Area of Science:

• Genetics
• Obstetrics
• Epidemiology

Background:

• Pre-eclampsia is a complex pregnancy disorder with a suspected polygenic basis.
• Identifying specific susceptibility genes and quantifying their associated risks has been challenging due to inconsistent findings in genetic association studies.

Purpose of the Study:

• To systematically review and meta-analyze genetic association studies on pre-eclampsia.
• To evaluate the evidence for associations between various candidate genes and pre-eclampsia risk.

Main Methods:

• Included 192 genetic association studies involving unrelated subjects and pre-eclampsia.
• Conducted meta-analyses for variants with at least three independent samples.
• Calculated summary odds ratios (ORs) and confidence intervals (CIs) using random effects models.

Main Results:

• Identified potential associations for F5 rs6025 (OR=1.74) and F2 rs1799963 (OR=1.72).
• These two associations demonstrated moderate epidemiological credibility.
• Small study size and poor reporting were identified as major sources of bias.

Conclusions:

• Current candidate gene studies have not established strong epidemiological credibility for pre-eclampsia associations.
• Large-scale replication of promising genetic variants and integration of high-throughput data are recommended to advance understanding of pre-eclampsia genetics.