Investigating the genetic basis of obstetrical diagnoses related to miscarriage and placental biology using genome-wide association study meta-analysis

Abstract

The triad of genetic, environmental and lifestyle factors contribute to adverse pregnancy outcomes. While the recent work investigating maternal genetic susceptibility to miscarriage has identified several genes involved in placental biology, the specific genetic risk factors of pregnancy complications remain poorly understood. To elucidate the maternal genetic basis of seven distinct obstetrical diagnoses related to miscarriage and placental biology, we conduct a case-control genome-wide association study meta-analysis using population-based data from the Estonian Biobank and the FinnGen study. We identify novel genomic risk loci and propose the most likely associated genes for diagnoses “haemorrhage in early pregnancy” and “premature rupture of membranes”. In addition, we estimate SNP- heritability, provide evidence of shared genetic background between the studied traits, and describe which other diagnoses are more common in women diagnosed with pregnancies with abortive outcomes and placenta-associated pregnancy complications.