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Int J Obes (Lond). 2018 Nov 21. doi: 10.1038/s41366-018-0249-0. [Epub ahead of print]

Maternal corticotropin-releasing hormone is associated with LEP DNA methylation at birth and in childhood: an epigenome-wide study in Project Viva.

Author information

1
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.
2
Department of Medical Statistics and Epidemiology, School of Public Health, Sun Yat-sen University, Guangzhou, Guangdong, China.
3
Department of Environmental Health Sciences, Columbia University Mailman School of Public Health, New York, NY, USA.
4
Channing Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA.
5
Connors Center for Women's Health and Gender Biology, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
6
Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.
7
Environmental Influences on Child Health Outcomes (ECHO) Office of the Director, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA.
8
Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA. MHIVERT@partners.org.
9
Diabetes Research Center, Massachusetts General Hospital, 50 Staniford Street, Boston, MA, USA. MHIVERT@partners.org.
10
Department of Medicine, Université de Sherbrooke, Sherbrooke, Québec, Canada. MHIVERT@partners.org.
11
Centre de recherche du Centre Hospitalier Universitaire de Sherbrooke, Sherbrooke, Québec, Canada. MHIVERT@partners.org.

Abstract

BACKGROUND:

Corticotropin-releasing hormone (CRH) plays a central role in regulating the secretion of cortisol which controls a wide range of biological processes. Fetuses overexposed to cortisol have increased risks of disease in later life. DNA methylation may be the underlying association between prenatal cortisol exposure and health effects. We investigated associations between maternal CRH levels and epigenome-wide DNA methylation of cord blood in offsprings and evaluated whether these associations persisted into mid-childhood.

METHODS:

We investigated mother-child pairs enrolled in the prospective Project Viva pre-birth cohort. We measured DNA methylation in 257 umbilical cord blood samples using the HumanMethylation450 Bead Chip. We tested associations of maternal CRH concentration with cord blood cells DNA methylation, adjusting the model for maternal age at enrollment, education, maternal race/ethnicity, maternal smoking status, pre-pregnancy body mass index, parity, gestational age at delivery, child sex, and cell-type composition in cord blood. We further examined the persistence of associations between maternal CRH levels and DNA methylation in children's blood cells collected at mid-childhood (n = 239, age: 6.7-10.3 years) additionally adjusting for the children's age at blood drawn.

RESULTS:

Maternal CRH levels are associated with DNA methylation variability in cord blood cells at 96 individual CpG sites (False Discovery Rate <0.05). Among the 96 CpG sites, we identified 3 CpGs located near the LEP gene. Regional analyses confirmed the association between maternal CRH and DNA methylation near LEP. Moreover, higher maternal CRH levels were associated with higher blood-cell DNA methylation of the promoter region of LEP in mid-childhood (P < 0.05, β = 0.64, SE = 0.30).

CONCLUSION:

In our cohort, maternal CRH was associated with DNA methylation levels in newborns at multiple loci, notably in the LEP gene promoter. The association between maternal CRH and LEP DNA methylation levels persisted into mid-childhood.

PMID:
30464231
DOI:
10.1038/s41366-018-0249-0

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