Abstract
Aberrant fetal growth is associated with morbidities and mortality during childhood and adult life. Although genetic and environmental factors are known to influence in utero growth, their relative contributions over pregnancy is unknown. We estimated, across gestation, the genetic heritability, contribution of shared environment, and genetic correlations of fetal growth measures (abdominal circumference (AC), humerus length (HL), femur length (FL), and estimated fetal weight (EFW)) in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies. Structural equation models were fit at the end of first trimester, during mid-gestation, late second trimester, and third trimester of pregnancy. The contribution of fetal genetics on fetal size increased with gestational age, peaking in late second trimester (AC = 53%, HL = 57%, FL = 72%, EFW = 71%; p < 0.05). In contrast, shared environment explained most of phenotypic variations in fetal growth in the first trimester (AC = 50%, HL = 54%, FL = 47%, EFW = 54%; p < 0.05), suggesting that the first trimester presents an intervention opportunity for a more optimal early fetal growth. Genetic correlations between growth traits (range 0.34–1.00; p < 0.05) were strongest at the end of first trimester and declined with gestation, suggesting that different fetal growth measures are more likely to be influenced by the same genes in early pregnancy.
Highlights
Estimates of heritability (h2), which measure the proportion of total phenotypic variance attributed to additive genetics[15], can be used to measure the extent to which fetal growth variations in a population can be explained by genetic effects[16]
Previous studies on heritability of fetal growth found that h2 of fetal growth varies over gestation, but the studies were limited to fetal anthropometry measured in late gestation and evaluated estimated fetal weight only[24,29]
The goal of this study was to examine the relative contributions of fetal additive genetic and environmental influences on fetal growth trajectories in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies project
Summary
Estimates of heritability (h2), which measure the proportion of total phenotypic variance attributed to additive genetics[15], can be used to measure the extent to which fetal growth variations in a population can be explained by genetic effects[16]. Twin studies are well suited for studying genetic and environmental influences on complex traits, because estimating the correlation between monozygotic (MZ) and dizygotic (DZ) twins allows measurement of the relative contributions of fetal additive genetic, shared environmental (c2) and non-shared environmental (e2) effects on the variance and covariance of fetal growth measures[16,17]. A comprehensive understanding of the fetal genetic and environmental influences on variance of a wide array of fetal growth measures will be pivotal to understand the pathobiology of fetal growth, to serve as a benchmark for estimating the missing heritability of previous and future genetic studies, and to inform effective targeting of biomedical interventions. The goal of this study was to examine the relative contributions of fetal additive genetic and environmental influences on fetal growth trajectories in a prospective cohort of dichorionic twin gestations recruited through the NICHD Fetal Growth Studies project. We estimated pair-wise genetic correlations between the fetal growth measures to gain insights on the extent to which the same genetic factor(s) influence different fetal growth measures during the progression of pregnancy
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