Abstract
Objective. Human birth weight variation has a significant genetic component and important clinical consequences. We performed a survey of single nucleotide polymorphisms (SNPs) in 14 candidate genes to identify associations with birth weight variation. Methods. SNP variation was surveyed in 221 healthy African–American mother-newborn pairs. Genes were selected based on previous association with obesity-related traits, significant differences in circulating protein levels in low birth weight pregnancies or association with newborn size in model organisms or growth disorders in humans. Association was tested via multiple linear regression with adjustment for significant covariables. Results. Under a dominant model SNP rs7754561 of ENPPI was significantly associated with birth weight. Among imprinted loci, maternal genotypes for SNP rs6026576 of GNAS were significantly associated with birth weight (additive and dominant models). This association was restricted to male offspring. Analyses that distinguished between alleles of paternal and maternal origin demonstrated that only maternally-transmitted alleles were associated with birth weight and that this association was restricted to male newborns. Conclusion. The effect of only maternally-transmitted alleles of GNAS may be a consequence of the complex splicing and imprinting pattern of the GNAS gene, although the reason this effect is observed only among male newborns is unclear.
Acknowledgements
We thank three anonymous reviewers for their helpful suggestions that improved the manuscript. This work was supported by grants to RMA from the National Institute of Child Health and Human Development (HD055462), the Children's Foundation Research Center of Memphis, the University of Tennessee Health Science Center's Clinical Translational Science Institute, and the Accredo Foundation. Support was also provided to GS from The Urban Child Institute to support the Conditions Affecting Neurocognitive Development and Learning in Early Childhood (CANDLE) study. Additional support was provided by a grant from the National Center for Research Resources (M01RR00211; University of Tennessee Health Science Center General Clinical Research Center). We gratefully acknowledge the laboratory expertise of Jeanette Peeples and the subject recruitment and sample collection by CANDLE staff.
Conflict of Interest statement
The authors declare no conflicts of interests, including patents, business relationships, or financial connections to funding sources. Sources of research funding: US National Institute of Child Health and Human Development (HD055462), Children's Foundation Research Center of Memphis, University of Tennessee Health Science Center's Clinical Translational Science Institute, Accredo Foundation, and The Urban Child Institute.
Declaration of interest: The authors alone are responsible for the content and writing of the paper.