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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 (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.

SUBMITTER: Ouidir M

PROVIDER: S-EPMC6885118 | biostudies-literature | 2019 Sep - Oct

REPOSITORIES: biostudies-literature

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

Ouidir Marion M Mendola Pauline P Workalemahu Tsegaselassie T Grewal Jagteshwar J Grantz Katherine L KL Zhang Cuilin C Wu Jing J Tekola-Ayele Fasil F

Journal of clinical lipidology 20190629 5

<h4>Background</h4>Fetal growth, an important predictor of cardiometabolic diseases in adults, is influenced by maternal and fetal genetic and environmental factors.<h4>Objective</h4>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).<h4>Methods</h4>We extracted genotype data for 2008 pregnant women recruited in the National Institute of Child Health and Human Development Fe ...[more]

PMID: 31383602

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Project description:BACKGROUND:Imprinted genes, which are expressed in a parent of origin-specific manner, are thought to mediate the genetic priorities of each parent in pregnancy. Recently we reported that some fetal imprinted gene variants are associated with maternal glucose concentrations and blood pressures in pregnancy. We suggest that the conflict between the effects of paternal and maternal transmitted genes starts at conception and may already be evident in measures of maternal metabolism in early pregnancy, before gestational diabetes is manifest. METHODS:Lipid fractions in maternal non-fasting serum collected around week 15 of pregnancy were profiled using direct infusion mass spectrometry in a subset Discovery Cohort (n =?200) of women from the Cambridge Baby Growth Study using direct infusion mass spectrometry. Associations between 151 haplotype-tag fetal polymorphisms in 16 imprinted genes and lipids were determined using partial least squares discriminant analysis. Variable importance in projection scores were used to identify those lipid species that contribute most to the underlying variation in the lipid profile and the concentrations of these species tested for associations with fetal imprinted gene alleles using linear regression. In an internal Validation Cohort (n =?567 women from the same cohort) the lipid fraction was profiled using liquid chromatography-mass spectrometry and tested for associations with the same fetal imprinted gene variants as above, followed by meta-analysis of associations from the Discovery and Validation Cohorts. RESULTS:The most significant associations were between a monounsaturated triglyceride (44:1) and both paternally-transmitted fetal H19 rs7950932 (R =?0.14, p =?2.9?×?10-?3, n =?386) and maternally-transmitted fetal FAM99A rs7131362 (R =?0.18, p =?6.2?×?10-?3, n =?351; association with maternal-untransmitted allele R =?0.08, p =?0.07, n =?328). This same triglyceride isoform was also associated with subsequent week 28 fasting glucose concentrations (R = 0.09, p = 9.9 × 10-?3, n = 673) and homeostasis model assessment of insulin resistance (R = 0.09, p = 0.01, n = 664). CONCLUSIONS:Fetal imprinted genes may influence maternal circulating clinically relevant triglyceride concentrations early in pregnancy.

Project description:Background and aimsIndividual macronutrient and micronutrient effects on placental growth have been widely investigated. However, the influence of overall maternal diet is relatively unknown. Therefore, the aim of this study is to examine associations between a range of maternal dietary scores during early pregnancy with placental outcomes, and to investigate whether there is evidence of sexual dimorphism.MethodsThis analysis of the Lifeways Cross-Generational Cohort includes 276 mother-child pairs. A validated 148-item semi-quantitative food frequency questionnaire assessed maternal diet in early pregnancy. Dietary scores reflecting dietary quality [Healthy Eating Index (HEI-2015), Dietary Approaches to Stop Hypertension (DASH)], dietary inflammatory potential [Dietary Inflammatory Index (DII) and the energy adjusted DII (E-DII)], dietary antioxidant status [Dietary Antioxidant Quality (DAQ)], and glycemic and insulinemic loads/indices (GL/GI, IL/II) were calculated. Linear regression analyses assessed maternal dietary score relationships with untrimmed placental weight (PW) and birth weight:placental weight (BW:PW) ratio.ResultsIn fully adjusted models, maternal E-DII and GI were positively associated, and HEI-2015 and DAQ were negatively associated with PW (B: 12.31, 95% CI: 0.41, 24.20, p = 0.04, B: 4.13, 95% CI: 0.10, 8.17, p = 0.04, B: -2.70, 95% CI: -5.03, -0.35, p = 0.02 and B: -15.03, 95% CI: -28.08, -1.98, p = 0.02, for E-DII, GI, HEI-2015 and DAQ respectively). Maternal DAQ associations with BW:PW ratio were attenuated. When stratified by sex, maternal GI and pregnancy-specific DAQ were associated with PW in female offspring (B: 5.61, 95% CI: 0.27, 10.96, p = 0.04 and B: -15.31, 95% CI: -30.35, -0.27, p = 0.046). Maternal E-DII and HEI-2015 were associated with PW in males (B: 24.31, 95% CI: 5.66, 42.96, p = 0.01 and B: -3.85, 95% CI: -7.47, -0.35, p = 0.03 respectively).ConclusionThe results of this novel investigation suggest that maternal diet may influence placental development. Female fetuses may be more sensitive to increased glucose levels whereas male fetuses may be more susceptible to in-utero stresses that are regulated by inflammatory pathways and overall diet quality. Hence, early pregnancy offers an opportune time for a mother to prioritize dietary changes that focus on reducing inflammatory and glycemic responses.

Dataset Information

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

Publications

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

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