Genetic survey of biomarkers at early and mid-pregnancy identifies pregnancy-specialized immune regulation

Much remains unknown about the genetics of immune system changes during pregnancy. We used SNP data in a pregnancy cohort to genetically investigate 47 immune biomarkers at two timepoints, along with change between timepoints (Δ). We identified 19 biomarkers with significant SNP-based heritability and 34 with genome-wide significant signals, demonstrating genetic regulation. The same biomarkers measured in early- and mid-pregnancy shared about half of significant associations across timepoints, with enrichment for immune pathways. In contrast, Δ showed enrichment in transcription factors and developmental processes. About half of suggestive associations overlapped with non-pregnancy associations. However, these data leave a substantial fraction of potentially timepoint-specific and pregnancy-unique findings. Nearby genes were enriched for high expression in decidual cells at the maternal-fetal interface, reinforcing the novelty of our results. We additionally explored the relationship between immune genetic associations and prior GWAS of pregnancy complications. Overall, we present the first two-timepoint genetic study of immune profile in pregnancy.