Race–ethnic differences in the associations of maternal lipid trait genetic risk scores with longitudinal fetal growth

Background: Fetal growth, an important predictor of cardiometabolic diseases in adults, is influenced by maternal and fetal genetic and environmental factors. Objective: We investigated the association between maternal lipid genetic risk score (GRS) and fetal growth among 4 US racial–ethnic populations (Whites, Blacks, Hispanics, and Asians). Methods: We extracted genotype data for 2008 pregnant women recruited in the National Institute of Child Health and Human Development Fetal Growth Studies—Singleton cohort with up to 6 standardized ultrasound examinations. GRS was calculated using 240 single-nucleotide polymorphisms previously associated with higher total cholesterol (GRS_TChol), low-density lipoprotein cholesterol (GRS_LDLc), and triglycerides (GRS_TG) and lower high-density lipoprotein cholesterol (GRS_HDLc). Results: At 40 weeks’ gestation, a unit increase in GRS_TG was associated with 11.4 g higher fetal weight (95% confidence interval [CI] 2.8–20.0 g) among normal-weight Whites, 26.3 g (95% CI 6.0–46.6 g) among obese Blacks, and 30.8 g (95% CI 6.3–55.3 g) among obese Hispanics. Higher GRS_HDLc was associated with increased fetal weight across 36 to 40 weeks among normal-weight Whites and across 13 to 20 weeks among normal-weight Asians, but with decreased fetal weight across 26 to 40 weeks among normal-weight Hispanics. Higher GRS_TChol was suggestively associated with increased fetal weight in males and decreased in females. Associations remained consistent after adjustment for serum lipids. Conclusion: Associations between fetal weight and maternal lipid GRS appear to vary by maternal race–ethnic group, obesity status, and offspring sex. Genetic susceptibility to unfavorable lipid profiles contributes to fetal growth differences even among normal-weight women suggesting a potential future application in predicting aberrant fetal growth.