Abstract
BackgroundThe birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities. The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race and birth weight. Data was collected on a cohort of 87 live born infants. IGF1 methylation was measured in DNA isolated from the mononuclear fraction of umbilical cord blood collected after delivery. Quantitative, loci-specific methylation was assessed using the Infinium HumanMethylation27 BeadArray (Illumina Inc., San Diego, CA). Locus specific methylation of the IGF1 CpG site was validated on a subset of the original sample (N = 61) using pyrosequencing. Multiple linear regression was used to examine relationships between IGF1 methylation, race, and birth weight. A formal mediation analysis was then used to estimate the relationship of IGF1 methylation to race and birth weight.ResultsBlack race was associated with a 7.45% decrease in gestational age-adjusted birth weight (aBW) (P = 0.04) and Black infants had significantly higher IGF1 methylation than non-Black infants (P < 0.05). A one standard deviation increase in IGF1 methylation was associated with a 3.32% decrease in aBW (P = 0.02). Including IGF1 methylation as a covariate, the effect of Black race on aBW was attenuated. A formal mediation analysis showed that the controlled direct effect of Black race on aBW was −6.26% (95% CI = −14.15, 1.06); the total effect of Black race on IGF1 methylation was −8.12% (95% CI = −16.08, −0.55); and the natural indirect effect of Black race on aBW through IGF1 methylation was −1.86% (95% CI = −5.22, 0.18)ConclusionThe results of the mediation analysis along with the multivariable regression analyses suggest that IGF1 methylation may partially mediate the relationship between Black race and aBW. Such epigenetic differences may be involved in racial disparities observed in perinatal outcomes.
Highlights
The birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts
Our analyses demonstrated that IGF1 methylation partially mediates the relationship between Black race and gestational ageadjusted birth weight
Consistent with many prior studies suggesting a relationship between variation in IGF1 expression and birth weight [15,17], our analyses suggest that the higher level of methylation of the IGF1 was significantly associated with a decrease in adjusted birth weight (aBW) (Table 3)
Summary
The birth weight of Black neonates in the United States is consistently smaller than that of their White counterparts. Epigenetic differences between the races may be involved in such disparities The goal of these analyses was to model the role of IGF1 methylation in mediating the association between race and birth weight. A formal mediation analysis was used to estimate the relationship of IGF1 methylation to race and birth weight. Black infants have consistently been shown to have smaller birth weights than their White counterparts [1]. DNA methylation profiles differ across African and European ancestral groups [8]. Both at birth and in adulthood, African-Americans have lower genome-wide
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