Methylation of the FGFR2 gene is associated with high birth weight centile in humans

Abstract

Aims: This study examined links between DNA methylation and birth weight centile (BWC), and explored the impact of genetic variation.

Materials & methods: Using HumanMethylation450 arrays, we examined candidate gene-associated CpGs in cord blood from newborns with low (<15th centile), medium (40-60th centile) and high (>85th centile) BWC (n = 12). Candidates were examined in an investigation cohort (n = 110) using pyrosequencing and genotyping for putative methylation-associated polymorphisms performed using standard PCR.

Results: Array analysis identified 314 candidate genes associated with BWC extremes, four of which showed ≥ 4 BWC-linked CpGs. Of these, PM20D1 and MI886 suggested genetically determined methylation levels. However, methylation at three CpGs in FGFR2 remained significantly associated with high BWC (p = 0.004-0.027).

Conclusion: We identified a novel biologically plausible candidate (FGFR2) for with BWC that merits further study.

Keywords: DNA methylation; FGFR2; birth weight centile; cord blood; epigenetic-genetic interactions.