DNA methylation in imprinted genes IGF2 and GNASXL is associated with prenatal maternal stress.
Epigenetic regulation of imprinted genes during embryonic development is influenced by the prenatal environment. Our aim was to examine the effect of maternal emotional stress and cortisol levels during pregnancy on methylation of imprinted genes, insulin-like growth factor 2 (IGF2) and guanine nucleotide-binding protein, alpha stimulating extra-large (GNASXL), using umbilical cord blood DNA. Maternal depressed mood (Edinburgh Depression Scale; EDS), pregnancy-related anxiety questionnaire (PRAQ) and cortisol day profiles were assessed throughout pregnancy. At birth, a cord blood sample (n = 80) was taken to study DNA methylation of IGF2 DMR0 (differentially methylated region), IGF2 anti-sense (IGF2AS) and GNASXL using Sequenom EpiTYPER. Linear mixed models were used to examine the relationship between DNA methylation and maternal stress, while correcting for confounders. We also studied the association of DNA methylation with the child ponderal index at birth. We found a cytosine-guanine dinucleotide (CpG)-specific association of PRAQ subscales with IGF2 DMR0 (CpG5, P < 0.0001) and GNASXL (CpG11, P = 0.0003), while IGF2AS was associated with maternal EDS scores (CpG33, P = 0.0003) and cortisol levels (CpG33, P = 0.0006; CpG37-38, P = 0.0005). However, there was no association of methylation with ponderal index at birth. In conclusion, maternal stress during pregnancy, as defined by cortisol measurements, EDS and PRAQ scores, is associated with DNA methylation of imprinted genes IGF2 and GNASXL. Our results provide further evidence that prenatal adversity can influence imprinted gene methylation, although future studies are needed to unravel the exact mechanisms.
Genetic Research about Stress and Psychiatry (GRASP), Department of Neurosciences, Leuven, Belgium.|Center for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
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Vangeel
Center for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
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Izzi
Genetic Research about Stress and Psychiatry (GRASP), Department of Neurosciences, Leuven, Belgium.|University Psychiatric Center, University of Leuven, Leuven, Belgium.
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Hompes
University Psychiatric Center, University of Leuven, Leuven, Belgium.
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Vansteelandt
Laboratory of Translational Genetics, Department of Oncology, University of Leuven, Leuven, Belgium.|Vesalius Research Center (VRC), VIB, Leuven, Belgium.
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Lambrechts
Center for Molecular and Vascular Biology (CMVB), Department of Cardiovascular Sciences, University of Leuven, Leuven, Belgium.
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Freson
Genetic Research about Stress and Psychiatry (GRASP), Department of Neurosciences, Leuven, Belgium.|University Psychiatric Center, University of Leuven, Leuven, Belgium.
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Claes
D000328:Adult; D002864:Chromogranins; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D005260:Female; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D018392:Genomic Imprinting; D006801:Humans; D007335:Insulin-Like Growth Factor II / Q000235:genetics*; D008297:Male; D011247:Pregnancy; D011248:Pregnancy Complications / Q000097:blood / Q000235:genetics* / Q000523:psychology; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics*; D013315:Stress, Psychological / Q000097:blood / Q000235:genetics* / Q000523:psychology; D011795:Surveys and Questionnaires
D002864:Chromogranins; C035170:IGF2 protein, human; D007335:Insulin-Like Growth Factor II; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs
Anxiety; DNA methylation; GNAS; IGF2; cortisol; depression; development; epigenetics; imprinting; prenatal stress