title: Racial differences in IGF1 methylation and birth weight.
abstract: BACKGROUND
  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. 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.
  
  
  RESULTS
  Black 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).
  
  
  CONCLUSIONS
  The 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.
authors.affiliation: Department of Family Medicine and Public Health Sciences, The Wayne State University School of Medicine, 3939 Woodward Avenue, Detroit, MI 48201 USA ; Current address: Department of Public Health Sciences, Henry Ford Hospital, One Ford Place, Detroit, MI 48202 USA.
authors.forename: Jennifer K
authors.initials: JK
authors.lastname: Straughen
authors.affiliation: Center for Molecular Medicine and Genetics, The Wayne State University School of Medicine, 540 East Canfield, Detroit, MI 48201 USA.
authors.forename: Levent
authors.initials: L
authors.lastname: Sipahi
authors.affiliation: Department of Psychology, University of Illinois at Urbana-Champaign, 603 E. Daniel Street, Champaign, IL 61820 USA.
authors.forename: Monica
authors.initials: M
authors.lastname: Uddin
authors.affiliation: Department of Family Medicine and Public Health Sciences, The Wayne State University School of Medicine, 3939 Woodward Avenue, Detroit, MI 48201 USA.
authors.forename: Dawn P
authors.initials: DP
authors.lastname: Misra
authors.affiliation: Department of Pediatrics, Division of Genetic and Metabolic Disorders, The Wayne State University School of Medicine, 3901 Beaubien Blvd, Detroit, MI 48201 USA ; Children's Hospital of Michigan, Division of Genetic and Metabolic Disorders, The Wayne State University School of Medicine, 3950 Beaubien Blvd, Detroit, MI 48201 USA.
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Misra
keywords: Birth weight; Disparities; Epigenetics; IGF1; Methylation; Perinatal; Race