Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age
The aim of this study was to identify placental DNA methylation (DNAm) variations associated with adiposity at 3 years of age. We quantified placental DNAm using the Infinium MethylationEPIC BeadChips. We assessed associations between DNAm at single-CpGs and skinfold thickness using robust linear re...
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| Format: | Article |
| Language: | English |
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MDPI AG
2020-09-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/19/7201 |
| _version_ | 1797552272428761088 |
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| author | Valérie Gagné-Ouellet Edith Breton Kathrine Thibeault Carol-Ann Fortin Véronique Desgagné Élise Girard Tremblay Andres Cardenas Renée Guérin Patrice Perron Marie-France Hivert Luigi Bouchard |
| author_facet | Valérie Gagné-Ouellet Edith Breton Kathrine Thibeault Carol-Ann Fortin Véronique Desgagné Élise Girard Tremblay Andres Cardenas Renée Guérin Patrice Perron Marie-France Hivert Luigi Bouchard |
| author_sort | Valérie Gagné-Ouellet |
| collection | DOAJ |
| description | The aim of this study was to identify placental DNA methylation (DNAm) variations associated with adiposity at 3 years of age. We quantified placental DNAm using the Infinium MethylationEPIC BeadChips. We assessed associations between DNAm at single-CpGs and skinfold thickness using robust linear regression models adjusted for gestational age, child’s sex, age at follow-up and cellular heterogeneity. We sought replication of DNAm association with child adiposity in an independent cohort. We quantified placental mRNA levels for annotated gene using qRT-PCR and tested for correlation with DNAm. Lower DNAm at cg22593959 and cg22436429 was associated with higher adiposity (<i>β</i> = −1.18, <i>q</i> = 0.002 and <i>β</i> = −0.82, <i>q</i> = 0.04). The cg22593959 is located in an intergenic region (chr7q31.3), whereas cg22436429 is within the <i>TFAP2E</i> gene (1p34.3). DNAm at cg22593959 and cg22436429 was correlated with mRNA levels at <i>FAM3C</i> (r<sub>s</sub> = −0.279, <i>p</i> = 0.005) and <i>TFAP2E</i> (r<sub>s</sub> = 0.216, <i>p</i> = 0.03). In an independent cohort, the association between placental DNAm at cg22593959 and childhood adiposity was of similar strength and direction (<i>β</i> = −3.8 ± 4.1, <i>p</i> = 0.36), yet non-significant. Four genomic regions were also associated with skinfold thickness within <i>FMN1</i>, <i>MAGI2</i>, <i>SKAP2</i> and <i>BMPR1B</i> genes. We identified placental epigenetic variations associated with adiposity at 3 years of age suggesting that childhood fat accretion patterns might be established during fetal life. |
| first_indexed | 2024-03-10T15:57:38Z |
| format | Article |
| id | doaj.art-32cb61a36ecc4c5395a369856524b717 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T15:57:38Z |
| publishDate | 2020-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-32cb61a36ecc4c5395a369856524b7172023-11-20T15:30:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-09-012119720110.3390/ijms21197201Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of AgeValérie Gagné-Ouellet0Edith Breton1Kathrine Thibeault2Carol-Ann Fortin3Véronique Desgagné4Élise Girard Tremblay5Andres Cardenas6Renée Guérin7Patrice Perron8Marie-France Hivert9Luigi Bouchard10Department of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDivision of Environmental Health Sciences, School of Public Health, University of California, Berkeley, CA 94720-7360, USADepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Medicine, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaDepartment of Biochemistry and Functional Genomics, Université de Sherbrooke, Sherbrooke, QC J1H 5N4, CanadaThe aim of this study was to identify placental DNA methylation (DNAm) variations associated with adiposity at 3 years of age. We quantified placental DNAm using the Infinium MethylationEPIC BeadChips. We assessed associations between DNAm at single-CpGs and skinfold thickness using robust linear regression models adjusted for gestational age, child’s sex, age at follow-up and cellular heterogeneity. We sought replication of DNAm association with child adiposity in an independent cohort. We quantified placental mRNA levels for annotated gene using qRT-PCR and tested for correlation with DNAm. Lower DNAm at cg22593959 and cg22436429 was associated with higher adiposity (<i>β</i> = −1.18, <i>q</i> = 0.002 and <i>β</i> = −0.82, <i>q</i> = 0.04). The cg22593959 is located in an intergenic region (chr7q31.3), whereas cg22436429 is within the <i>TFAP2E</i> gene (1p34.3). DNAm at cg22593959 and cg22436429 was correlated with mRNA levels at <i>FAM3C</i> (r<sub>s</sub> = −0.279, <i>p</i> = 0.005) and <i>TFAP2E</i> (r<sub>s</sub> = 0.216, <i>p</i> = 0.03). In an independent cohort, the association between placental DNAm at cg22593959 and childhood adiposity was of similar strength and direction (<i>β</i> = −3.8 ± 4.1, <i>p</i> = 0.36), yet non-significant. Four genomic regions were also associated with skinfold thickness within <i>FMN1</i>, <i>MAGI2</i>, <i>SKAP2</i> and <i>BMPR1B</i> genes. We identified placental epigenetic variations associated with adiposity at 3 years of age suggesting that childhood fat accretion patterns might be established during fetal life.https://www.mdpi.com/1422-0067/21/19/7201skinfolds thicknessepigeneticsfetal programmingDNA methylationtranscriptomicsEPIC array |
| spellingShingle | Valérie Gagné-Ouellet Edith Breton Kathrine Thibeault Carol-Ann Fortin Véronique Desgagné Élise Girard Tremblay Andres Cardenas Renée Guérin Patrice Perron Marie-France Hivert Luigi Bouchard Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age International Journal of Molecular Sciences skinfolds thickness epigenetics fetal programming DNA methylation transcriptomics EPIC array |
| title | Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age |
| title_full | Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age |
| title_fullStr | Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age |
| title_full_unstemmed | Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age |
| title_short | Placental Epigenome-Wide Association Study Identified Loci Associated with Childhood Adiposity at 3 Years of Age |
| title_sort | placental epigenome wide association study identified loci associated with childhood adiposity at 3 years of age |
| topic | skinfolds thickness epigenetics fetal programming DNA methylation transcriptomics EPIC array |
| url | https://www.mdpi.com/1422-0067/21/19/7201 |
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