Dataset Information

HIF3A association with adiposity: the story begins before birth.

ABSTRACT:

Aim

Determine if the association of HIF3A DNA methylation with weight and adiposity is detectable early in life.

Material & methods

We determined HIF3A genotype and DNA methylation patterns (on hybridization arrays) in DNA extracted from umbilical cords of 991 infants. Methylation levels at three CpGs in the HIF3A first intron were related to neonatal and infant anthropometry and to genotype at nearby polymorphic sites.

Results & conclusion

Higher methylation levels at three previously described HIF3A CpGs were associated with greater infant weight and adiposity. The effect sizes were slightly smaller than those reported for adult BMI. There was also an interaction within cis-genotype. The association between higher DNA methylation at HIF3A and increased adiposity is present in neonates. In this study, no particular prenatal factor strongly influenced HIF3A hypermethylation. Our data nonetheless suggest shared prenatal influences on HIF3A methylation and adiposity.

SUBMITTER: Pan H

PROVIDER: S-EPMC4863876 | biostudies-literature | 2015

REPOSITORIES: biostudies-literature

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Publications

HIF3A association with adiposity: the story begins before birth.

Pan Hong H Lin Xinyi X Wu Yonghui Y Chen Li L Teh Ai Ling AL Soh Shu E SE Lee Yung Seng YS Tint Mya Thway MT MacIsaac Julia L JL Morin Alexander M AM Tan Kok Hian KH Yap Fabian F Saw Seang Mei SM Kobor Michael S MS Meaney Michael J MJ Godfrey Keith M KM Chong Yap-Seng YS Gluckman Peter D PD Karnani Neerja N Holbrook Joanna D JD

Epigenomics 20150526 6

<h4>Aim</h4>Determine if the association of HIF3A DNA methylation with weight and adiposity is detectable early in life.<h4>Material & methods</h4>We determined HIF3A genotype and DNA methylation patterns (on hybridization arrays) in DNA extracted from umbilical cords of 991 infants. Methylation levels at three CpGs in the HIF3A first intron were related to neonatal and infant anthropometry and to genotype at nearby polymorphic sites.<h4>Results & conclusion</h4>Higher methylation levels at thre ...[more]

PMID: 26011824

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Project description:BackgroundObesity is an escalating health problem worldwide, and hence the causes underlying its development are of primary importance to public health. There is growing evidence that suboptimal intrauterine environment can perturb the metabolic programing of the growing fetus, thereby increasing the risk of developing obesity in later life. However, the link between early exposures in the womb, genetic susceptibility, and perturbed epigenome on metabolic health is not well understood. In this study, we shed more light on this aspect by performing a comprehensive analysis on the effects of variation in prenatal environment, neonatal methylome, and genotype on birth weight and adiposity in early childhood.MethodsIn a prospective mother-offspring cohort (N = 987), we interrogated the effects of 30 variables that influence the prenatal environment, umbilical cord DNA methylation, and genotype on offspring weight and adiposity, over the period from birth to 48 months. This is an interim analysis on an ongoing cohort study.ResultsEleven of 30 prenatal environments, including maternal adiposity, smoking, blood glucose and plasma unsaturated fatty acid levels, were associated with birth weight. Polygenic risk scores derived from genetic association studies on adult adiposity were also associated with birth weight and child adiposity, indicating an overlap between the genetic pathways influencing metabolic health in early and later life. Neonatal methylation markers from seven gene loci (ANK3, CDKN2B, CACNA1G, IGDCC4, P4HA3, ZNF423 and MIRLET7BHG) were significantly associated with birth weight, with a subset of these in genes previously implicated in metabolic pathways in humans and in animal models. Methylation levels at three of seven birth weight-linked loci showed significant association with prenatal environment, but none were affected by polygenic risk score. Six of these birth weight-linked loci continued to show a longitudinal association with offspring size and/or adiposity in early childhood.ConclusionsThis study provides further evidence that developmental pathways to adiposity begin before birth and are influenced by environmental, genetic and epigenetic factors. These pathways can have a lasting effect on offspring size, adiposity and future metabolic outcomes, and offer new opportunities for risk stratification and prevention of obesity.Clinical trial registrationThis birth cohort is a prospective observational study, designed to study the developmental origins of health and disease, and was retrospectively registered on 1 July 2010 under the identifier NCT01174875 .

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Dataset Information

HIF3A association with adiposity: the story begins before birth.

Aim

Material & methods

Results & conclusion

Publications

HIF3A association with adiposity: the story begins before birth.

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