Highlights
- •Genetic risk score (GRS) and fetal weight (FW) associations vary by race–ethnicity, body mass index, and fetal sex.
- •GRS for triglycerides was associated with increased FW in normal-weight Whites and obese Blacks.
- •GRS for high-density lipoprotein cholesterol increased FW in normal-weight Whites and Asians but decreased in Hispanics.
- •GRS for total cholesterol was associated with increased FW in males and decreased in females.
- •Results suggests that the GRS for low-density lipoprotein cholesterol may operate by modulating circulating low-density lipoprotein cholesterol.
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 (GRSTChol), low-density lipoprotein cholesterol (GRSLDLc), and triglycerides (GRSTG) and lower high-density lipoprotein cholesterol (GRSHDLc).
Results
At 40 weeks’ gestation, a unit increase in GRSTG 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 GRSHDLc 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 GRSTChol 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
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Article info
Publication history
Published online: June 29, 2019
Accepted:
June 24,
2019
Received:
December 3,
2018
Footnotes
Clinical Trial Registration: ClinicalTrials.gov, NCT00912132.
Identification
Copyright
Published by Elsevier Inc. on behalf of National Lipid Association.
