Placental expression quantitative trait loci in an East Asian population

Expression quantitative trait loci (eQTL) analysis measures the contribution of genetic variation in gene expression on complex traits. Although this methodology has been used to examine gene regulation in numerous human tissues, eQTL research in solid tissues is relatively lacking. We conducted eQTL analysis on placentas collected from an East Asian population in an effort to identify gene regulatory mechanisms in this tissue. Placentas (n 1/4 102) were collected at the time of cesarean delivery. mRNA was extracted, sequenced with NGS, and compared with matched maternal and fetal DNA arrays performed using maternal and neonatal cord blood. Linear regression modeling was performed using tensorQTL. Fine-mapping along with epigenomic annotation was used to select putative functional variants. We identified 2,703 coding genes that contained at least one eQTL with statistical significance (false discovery rate <0.05). After fine-mapping, we found 108 previously unreported eQTL variants with posterior inclusion probability >0.1. Of these, 19% were located in genomic regions with evidence from public placental epigenome suggesting that they may be functionally relevant. For example, variant rs28379289 located in the placenta-specific regulatory region changes the binding affinity of transcription factor leading to higher expression of LGALS3, which is known to affect placental function. This study expands the knowledge base of regulatory elements within the human placenta and identifies 108 previously unreported placenta eQTL signals, which are listed in our publicly available GMI eQTL database. Further studies are needed to identify and characterize genetic regulatory mechanisms that affect placental function in normal pregnancy and placenta-related diseases.