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

Abstract

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.

Keywords: Birth weight; Fetal growth; Genetic risk score; Maternal lipid traits.

Figure 1:

Estimated fetal weight (EFW) change (in Z-score) for each 5 unit increase in the GRS_HDLc and GRS_TG stratified by pre-pregnancy BMI (N=2,008 from the NICHD Fetal Growth Studies – Singleton cohort). Middle black solid-lines represent the adjusted change in Z-score; top and bottom dash-lines represent upper and lower 95% confidence interval, respectively; red solid-lines represent the NULL estimates. Adjusted for maternal age, pre-pregnancy BMI, highest level of education, marital status, parity, gestational age at delivery, offspring sex, diabetes, pregnancy-related hypertensive diseases and for the first five genetic principal components.

Figure 2:

Estimated fetal weight change (in Z-score) for each 5 unit increase in the GRS_TChol stratified by offspring sex (N=2,008 from the NICHD Fetal Growth Studies – Singleton cohort). Middle black solid-lines represent the adjusted change in Z-score; top and bottom dash-lines represent upper and lower 95% confidence interval, respectively; red solid-lines represent the NULL estimates. Adjusted for maternal age, pre-pregnancy BMI, highest level of education, marital status, parity, gestational age at delivery, offspring sex, diabetes, pregnancy-related hypertensive diseases and for the first five genetic principal components.