- •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.
Fetal growth, an important predictor of cardiometabolic diseases in adults, is influenced by maternal and fetal genetic and environmental factors.
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).
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).
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.
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.
To read this article in full you will need to make a payment
Purchase one-time access:Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
One-time access price info
- For academic or personal research use, select 'Academic and Personal'
- For corporate R&D use, select 'Corporate R&D Professionals'
Subscribe:Subscribe to Journal of Clinical Lipidology
Already a print subscriber? Claim online access
Already an online subscriber? Sign in
Register: Create an account
Institutional Access: Sign in to ScienceDirect
- The intrauterine origins of cardiovascular disease.Acta Paediatr. 1993; 82: 93-99
- Maternal triglyceride levels during early pregnancy are associated with birth weight and postnatal growth.J Pediatr. 2011; 159: 736-742.e1
- Maternal anthropometric and metabolic factors in the first half of pregnancy and risk of neonatal macrosomia in term pregnancies. A prospective study.Eur J Endocrinol. 2005; 153: 887-894
- Maternal serum triglyceride at 24--32 weeks' gestation and newborn weight in nondiabetic women with positive diabetic screens.Obstet Gynecol. 2001; 97: 776-780
- Association of maternal serum lipids at late gestation with the risk of neonatal macrosomia in women without diabetes mellitus.Lipids Health Dis. 2018; 17: 78
- Genome-wide association study of offspring birth weight in 86 577 women identifies five novel loci and highlights maternal genetic effects that are independent of fetal genetics.Hum Mol Genet. 2018; 27: 742-756
- A genome-wide association study for blood lipid phenotypes in the Framingham Heart Study.BMC Med Genet. 2007; 8: S17
- Genome-wide association analysis of metabolic traits in a birth cohort from a founder population.Nat Genet. 2009; 41: 35-46
- Pleiotropic meta-analyses of longitudinal studies discover novel genetic variants associated with age-related diseases.Front Genet. 2016; 7: 179
- A bivariate genome-wide approach to metabolic syndrome: STAMPEED consortium.Diabetes. 2011; 60: 1329-1339
- Placental LPL gene expression is increased in severe intrauterine growth-restricted pregnancies.Pediatr Res. 2006; 59: 250-253
- Maternal apolipoprotein E genotype as a potential risk factor for poor birth outcomes: The Bogalusa Heart Study.J Perinatol. 2016; 36: 432-438
- Diet and lifestyle interventions on lipids: combination with genomics and metabolomics.Clin Lipidol. 2014; 9: 417-427
- Gene-diet interaction and plasma lipid response to dietary intervention.Curr Atheroscler Rep. 2001; 3: 200-208
- A large electronic-health-record-based genome-wide study of serum lipids.Nat Genet. 2018; 50: 401-413
- Prepregnancy body mass index and gestational age-dependent changes in lipid levels during pregnancy.Obstet Gynecol. 2010; 116: 107-113
- The impact of preconceptional obesity on trajectories of maternal lipids during gestation.Sci Rep. 2016; 6: 29971
- Maternal obesity modulates intracellular lipid turnover in the human term placenta.Int J Obes (lond). 2017; 41: 317-323
- Maternal and fetal blood lipid concentrations during pregnancy differ by maternal body mass index: findings from the ROLO study.BMC Pregnancy Childbirth. 2017; 17: 360
- Sex differences in lipid and lipoprotein metabolism.Mol Metab. 2018; 15: 45-55
- Biological, clinical and population relevance of 95 loci for blood lipids.Nature. 2010; 466: 707-713
- Discovery and refinement of loci associated with lipid levels.Nat Genet. 2013; 45: 1274-1283
- Cohort profile: NICHD fetal growth studies-singletons and twins.Int J Epidemiol. 2018; 47 (25–25I)
- Racial/ethnic standards for fetal growth: the NICHD fetal growth studies.Am J Obstet Gynecol. 2015; 213: 449.e1-449.e41
- Next-generation genotype imputation service and methods.Nat Genet. 2016; 48: 1284-1287
- Reference-based phasing using the Haplotype Reference Consortium panel.Nat Genet. 2016; 48: 1443-1448
- minimac2: faster genotype imputation.Bioinformatics. 2015; 31: 782-784
- A global reference for human genetic variation.Nature. 2015; 526: 68-74
- Plasma concentrations of lipids during pregnancy and the risk of gestational diabetes mellitus: a longitudinal study.J Diabetes. 2018; 10: 487-495
- Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge.Clin Chem. 1972; 18: 499-502
- Ultrasound quality assurance for singletons in the National Institute of Child Health and Human Development Fetal Growth Studies.J Ultrasound Med. 2016; 35: 1725-1733
- 23: Can sonographer education and image review standardize image acquisition and caliper placement in 2D ultrasounds? Experience from the NICHD Fetal Growth Study.Am J Obstet Gynecol. 2012; 206: S15-S16
- Estimation of fetal weight with the use of head, body, and femur measurements--a prospective study.Am J Obstet Gynecol. 1985; 151: 333-337
- A revised birth weight reference for the United States.Obstet Gynecol. 2014; 124: 16-22
- Genetic dissection of complex traits.Science. 1994; 265: 2037-2048
- Principal components analysis corrects for stratification in genome-wide association studies.Nat Genet. 2006; 38: 904-909
- Second-generation PLINK: rising to the challenge of larger and richer datasets.Gigascience. 2015; 4: 7
- Optimal serum cotinine levels for distinguishing cigarette smokers and nonsmokers within different racial/ethnic groups in the United States between 1999 and 2004.Am J Epidemiol. 2009; 169: 236-248
- Changes in serum lipid levels during pregnancy and association with neonatal outcomes: a large cohort study.Reprod Sci. 2018; 25: 1406-1412
- Lipid and lipoprotein concentrations in pregnancies complicated by intrauterine growth restriction.J Clin Endocrinol Metab. 1999; 84: 128-130
- New genetic loci link adipose and insulin biology to body fat distribution.Nature. 2015; 518: 187-196
- Meta-analysis of genome-wide association studies in >80 000 subjects identifies multiple loci for C-reactive protein levels.Circulation. 2011; 123: 731-738
- Bivariate genome-wide association study identifies novel pleiotropic loci for lipids and inflammation.BMC Genomics. 2016; 17: 443
- Genomewide meta-analysis identifies loci associated with IGF-I and IGFBP-3 levels with impact on age-related traits.Aging Cell. 2016; 15: 811-824
- Maternal lipids associated with large-for-gestational-age birth weight in women with type 1 diabetes: results from a prospective single-center study.Arch Med Sci. 2017; 13: 753-759
- Maternal lipids and leptin concentrations are associated with large-for-gestational-age births: a prospective cohort study.Sci Rep. 2017; 7: 804
- Associations between maternal lipid profile and pregnancy complications and perinatal outcomes: a population-based study from China.BMC Pregnancy Childbirth. 2016; 16: 60
- High burden of birthweight-lowering genetic variants in Africans and Asians.BMC Med. 2018; 16: 70
- Genetic determinants of lipid traits in diverse populations from the population architecture using genomics and epidemiology (PAGE) study.PLoS Genet. 2011; 7: e1002138
- Prepregnancy body mass index influences lipid oxidation rate during pregnancy.Acta Obstet Gynecol Scand. 2017; 96: 207-215
- Pregnancy outcomes in familial hypercholesterolemia: a registry-based study.Circulation. 2011; 124: 1606-1614
- Maternal lipid profile during early pregnancy and pregnancy complications and outcomes: the ABCD study.J Clin Endocrinol Metab. 2012; 97: 3917-3925
- Sex differences in obesity, lipid metabolism, and inflammation-A role for the sex chromosomes?.Mol Metab. 2018; 15: 35-44
- Genetic basis for sex differences in obesity and lipid metabolism.Annu Rev Nutr. 2017; 37: 225-245
- Heritability of metabolic syndrome traits in a large population-based sample.J Lipid Res. 2013; 54: 2914-2923
- Variants close to NTRK2 gene are associated with birth weight in female twins.Twin Res Hum Genet. 2014; 17: 254-261
- Factors affecting fetal growth and body composition.Am J Obstet Gynecol. 1995; 172: 1459-1463
- Androgens and fetal growth.Horm Res. 1998; 50: 243-244
- Maternal non-glycemic contributors to fetal growth in obesity and gestational diabetes: spotlight on lipids.Curr Diab Rep. 2018; 18: 37
- Human demographic history impacts genetic risk prediction across diverse populations.Am J Hum Genet. 2017; 100: 635-649
Published online: June 29, 2019
Accepted: June 24, 2019
Received: December 3, 2018
Clinical Trial Registration: ClinicalTrials.gov, NCT00912132.
Published by Elsevier Inc. on behalf of National Lipid Association.