A rapid review of genetic association studies of parent-of-origin effects and fetal growth

Genetic factors contribute, in part, to fetal growth restriction (FGR), a developmental condition of disrupted fetal development associated with serious health consequences. Among these factors, variants that display parent-of-origin effects (POE) may play a significant role in the variation of human fetal growth. We conducted a synthesis of the available evidence on genetic associations between POE variants and fetal growth traits, aiming to summarize identified variants and compare study designs. Literature searches were performed on the Ovid research platform using the bibliographic databases MEDLINE and Embase, identifying 17 genetic association studies that reported 38 study-wide significant POE variants associated with one or more fetal growth trait(s). Candidate gene approaches were dominant among the studies identified (n = 13), but the application of genome-wide association studies (GWAS) continues to expand as computational phasing and POE determination methods have advanced. While genetic association studies are useful for identifying POE variants, low replication of findings among independent studies remains a major hindrance to validation. Birth weight was the most common measure of fetal growth among our identified studies (n = 15). Further research is needed on alternative measures of fetal growth. Additionally, most of the studies were conducted in sample populations of White European ancestry (n = 9), indicating a gap in research among more diverse populations. Genetic association studies have provided evidence that POE variants contribute to fetal growth variation, encouraging further investigations into the genetic regulation and biological mechanisms underlying fetal growth.