DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence
Obesity is associated with higher cardio-metabolic risk even in childhood and adolescence; whether this association is mediated by epigenetic mechanisms remains unclear. We examined the extent to which mid-childhood body mass index (BMI) z-score (median age 7.7 years) was associated with cardio-meta...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2018-11-01
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| Series: | Epigenetics |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/15592294.2018.1543503 |
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| author | Jian V. Huang Andres Cardenas Elena Colicino C. Mary Schooling Sheryl L. Rifas-Shiman Golareh Agha Yinan Zheng Lifang Hou Allan C. Just Augusto A. Litonjua Dawn L. DeMeo Xihong Lin Emily Oken Marie-France Hivert Andrea A. Baccarelli |
| author_facet | Jian V. Huang Andres Cardenas Elena Colicino C. Mary Schooling Sheryl L. Rifas-Shiman Golareh Agha Yinan Zheng Lifang Hou Allan C. Just Augusto A. Litonjua Dawn L. DeMeo Xihong Lin Emily Oken Marie-France Hivert Andrea A. Baccarelli |
| author_sort | Jian V. Huang |
| collection | DOAJ |
| description | Obesity is associated with higher cardio-metabolic risk even in childhood and adolescence; whether this association is mediated by epigenetic mechanisms remains unclear. We examined the extent to which mid-childhood body mass index (BMI) z-score (median age 7.7 years) was associated with cardio-metabolic risk score in early adolescence (median age 12.9 years) via mid-childhood DNA methylation among 265 children in the Project Viva. We measured DNA methylation in leukocytes using the Infinium Human Methylation450K BeadChip. We assessed mediation CpG-by-CpG using epigenome-wide association analyses, high-dimensional mediation analysis, and natural effect models. We observed mediation by mid-childhood DNA methylation at 6 CpGs for the association between mid-childhood BMI z-score and cardio-metabolic risk score in early adolescence in the high-dimensional mediation analysis (accounting for 10% of the total effect) and in the natural effect model (β = 0.04, P = 3.2e-2, accounting for 13% of the total effect). The natural direct effect of BMI z-score on cardio-metabolic risk score was still evident (β = 0.27, P = 1.1e-25). We also observed mediation by mid-childhood DNA methylation at 5 CpGs that was in the opposite direction from the total effect (natural effect model: β = −0.04, P = 2.0e-2). Mediation in different directions implies a complex role of DNA methylation in the association between BMI and cardio-metabolic risk and needs further investigation. Future studies with larger sample size and greater variability in cardio-metabolic risk will further help elucidate the role of DNA methylation for cardio-metabolic risk. |
| first_indexed | 2024-03-11T23:07:02Z |
| format | Article |
| id | doaj.art-fd3b4a2a409646eb9c50e1faa91e7c5a |
| institution | Directory Open Access Journal |
| issn | 1559-2294 1559-2308 |
| language | English |
| last_indexed | 2024-03-11T23:07:02Z |
| publishDate | 2018-11-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Epigenetics |
| spelling | doaj.art-fd3b4a2a409646eb9c50e1faa91e7c5a2023-09-21T13:09:21ZengTaylor & Francis GroupEpigenetics1559-22941559-23082018-11-011310-111072108710.1080/15592294.2018.15435031543503DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescenceJian V. Huang0Andres Cardenas1Elena Colicino2C. Mary Schooling3Sheryl L. Rifas-Shiman4Golareh Agha5Yinan Zheng6Lifang Hou7Allan C. Just8Augusto A. Litonjua9Dawn L. DeMeo10Xihong Lin11Emily Oken12Marie-France Hivert13Andrea A. Baccarelli14Columbia Mailman School of Public HealthHarvard Medical School and Harvard Pilgrim Health Care InstituteIcahn School of Medicine at Mount SinaiThe University of Hong KongHarvard Medical School and Harvard Pilgrim Health Care InstituteColumbia Mailman School of Public HealthCenter for Population Epigenetics, Feinberg School of Medicine, Northwestern UniversityNorthwestern UniversityIcahn School of Medicine at Mount SinaiUniversity of Rochester Medical CenterBrigham and Women’s HospitalHarvard UniversityHarvard Medical School and Harvard Pilgrim Health Care InstituteHarvard Medical School and Harvard Pilgrim Health Care InstituteColumbia Mailman School of Public HealthObesity is associated with higher cardio-metabolic risk even in childhood and adolescence; whether this association is mediated by epigenetic mechanisms remains unclear. We examined the extent to which mid-childhood body mass index (BMI) z-score (median age 7.7 years) was associated with cardio-metabolic risk score in early adolescence (median age 12.9 years) via mid-childhood DNA methylation among 265 children in the Project Viva. We measured DNA methylation in leukocytes using the Infinium Human Methylation450K BeadChip. We assessed mediation CpG-by-CpG using epigenome-wide association analyses, high-dimensional mediation analysis, and natural effect models. We observed mediation by mid-childhood DNA methylation at 6 CpGs for the association between mid-childhood BMI z-score and cardio-metabolic risk score in early adolescence in the high-dimensional mediation analysis (accounting for 10% of the total effect) and in the natural effect model (β = 0.04, P = 3.2e-2, accounting for 13% of the total effect). The natural direct effect of BMI z-score on cardio-metabolic risk score was still evident (β = 0.27, P = 1.1e-25). We also observed mediation by mid-childhood DNA methylation at 5 CpGs that was in the opposite direction from the total effect (natural effect model: β = −0.04, P = 2.0e-2). Mediation in different directions implies a complex role of DNA methylation in the association between BMI and cardio-metabolic risk and needs further investigation. Future studies with larger sample size and greater variability in cardio-metabolic risk will further help elucidate the role of DNA methylation for cardio-metabolic risk.http://dx.doi.org/10.1080/15592294.2018.1543503obesitybmicardio-metabolicdna methylationepigeneticsmediation |
| spellingShingle | Jian V. Huang Andres Cardenas Elena Colicino C. Mary Schooling Sheryl L. Rifas-Shiman Golareh Agha Yinan Zheng Lifang Hou Allan C. Just Augusto A. Litonjua Dawn L. DeMeo Xihong Lin Emily Oken Marie-France Hivert Andrea A. Baccarelli DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence Epigenetics obesity bmi cardio-metabolic dna methylation epigenetics mediation |
| title | DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence |
| title_full | DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence |
| title_fullStr | DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence |
| title_full_unstemmed | DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence |
| title_short | DNA methylation in blood as a mediator of the association of mid-childhood body mass index with cardio-metabolic risk score in early adolescence |
| title_sort | dna methylation in blood as a mediator of the association of mid childhood body mass index with cardio metabolic risk score in early adolescence |
| topic | obesity bmi cardio-metabolic dna methylation epigenetics mediation |
| url | http://dx.doi.org/10.1080/15592294.2018.1543503 |
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