A polygenic growth score and risk for large for gestational age birth weight

Abstract Context Large for gestational age (LGA) birth weight is associated with both short- and long-term health consequences for offspring, and fetal genetics may contribute to risk for LGA birth weight. Objectives We evaluated the relationship between a polygenic growth score (PGS) and LGA birth weight in relation to maternal characteristics. Design A previously developed PGS for LGA birth weight was calculated using offspring DNA. We evaluated the relationship between tertiles of the PGS, maternal body mass index, and glycemia assessed by the 50-gram glucose challenge test on the risk for LGA birth weight using 1-way ANOVA and chi-squared tests as well as a regularized linear model. Participants Nulliparous individuals recruited from 8 clinical sites in the United States. Main Outcome Measures LGA birth weight. Results Infant genotype was available for 3286 individuals. A PGS in the first tertile was associated with a lower risk [adjusted odds ratio (aOR) 0.71, 95% confidence interval (CI) 0.53-0.94], and the third tertile with a higher risk (aOR 1.29, 95% CI 1.02-1.63) for LGA birth weight. The odds of LGA birth weight were highest in those with maternal body mass index (BMI) ≥35 kg/m2 and a PGS of either the second tertile (odds ratio 3.54, 95% CI 1.96-6.38) or third tertile (odds ratio 2.69, 95% CI 1.54-4.71). Conclusion A PGS may assist with identification of those fetuses at increased risk for LGA birth weight, particularly among individuals with a BMI ≥35 kg/m2.