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::

•  birth weight centile
• cord blood
• DNA methylation
• epigenetic-genetic interactions
• FGFR2

Financial & competing interests disclosure

The authors gratefully acknowledge financial support from the World Cancer Research Fund (ref. 2008/15; to WE Farrell AA Fryer, RD Emes WD Carroll and KMK Ismail). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

The authors gratefully acknowledge financial support from the World Cancer Research Fund (ref. 2008/15; to WE Farrell AA Fryer, RD Emes WD Carroll and KMK Ismail). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.