Genetic polymorphisms associated with adverse pregnancy outcomes in nulliparas

Area of Science:

• Genetics and Genomics
• Reproductive Medicine
• Maternal-Fetal Medicine

Background:

• Adverse pregnancy outcomes (APOs) contribute significantly to global maternal and infant morbidity and mortality.
• The underlying pathophysiology of APOs remains largely unknown, hindering effective prevention and treatment strategies.
• Genetic factors are suspected to play a role in maternal susceptibility to APOs.

Purpose of the Study:

• To identify genetic risk markers associated with four adverse pregnancy outcomes: pregnancy loss, gestational length, gestational diabetes, and preeclampsia.
• To leverage multi-ancestry genome-wide association studies (GWAS) to uncover novel genetic associations.

Main Methods:

• Performed multi-ancestry genome-wide association studies (GWAS) for pregnancy loss, gestational length, gestational diabetes, and preeclampsia.
• Clustered participants by genetic ancestry into European, African, and Admixed American sub-cohorts for focused analysis.
• Conducted association tests within each sub-cohort and performed meta-analysis to combine results.

Main Results:

• Identified two novel loci associated with increased risk of pregnancy loss (near TRMU and RGMA).
• Discovered two new variants linked to gestational length (near WFDC1 and AC005052.1).
• Found three novel loci associated with gestational diabetes (near ZBTB20, GUCY1A2, and RPL7P20).
• Confirmed associations of fourteen previously identified loci with related outcomes like preterm birth and preeclampsia.

Conclusions:

• This GWAS meta-analysis successfully identified several novel genetic loci associated with adverse pregnancy outcomes.
• The findings provide new insights into the genetic architecture of pregnancy complications, paving the way for future research.
• Further investigation into these genetic markers may lead to improved risk prediction and targeted interventions for APOs.