Effect of parental adverse childhood experiences on intergenerational DNA methylation signatures from peripheral blood mononuclear cells and buccal mucosa

Sahra Mohazzab-Hosseinian; Erika Garcia; Joseph Wiemels; Crystal Marconett; Karina Corona; Caitlin G Howe; Helen Foley; Shohreh F Farzan; Theresa M Bastain; Carrie V Breton

doi:10.1038/s41398-024-02747-9

Effect of parental adverse childhood experiences on intergenerational DNA methylation signatures from peripheral blood mononuclear cells and buccal mucosa

Transl Psychiatry. 2024 Feb 12;14(1):89. doi: 10.1038/s41398-024-02747-9.

Authors

Affiliations

¹ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. mohazzab@usc.edu.
² Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
³ Center for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁴ Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁵ Hastings Center for Pulmonary Research, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁶ Norris Comprehensive Cancer Center, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁷ Surgery, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁸ Biochemistry and Molecular Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA.
⁹ Geisel School of Medicine at Dartmouth, 1 Medical Center Dr, Lebanon, NH, 03756, USA.
¹⁰ Department of Population and Public Health Sciences, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90033, USA. breton@usc.edu.

Abstract

In this study, the effect of cumulative ACEs experienced on human maternal DNA methylation (DNAm) was estimated while accounting for interaction with domains of ACEs in prenatal peripheral blood mononuclear cell samples from the Maternal and Developmental Risks from Environmental Stressors (MADRES) pregnancy cohort. The intergenerational transmission of ACE-associated DNAm was also explored used paired maternal (N = 120) and neonatal cord blood (N = 69) samples. Replication in buccal samples was explored in the Children's Health Study (CHS) among adult parental (N = 31) and pediatric (N = 114) samples. We used a four-level categorical indicator variable for ACEs exposure: none (0 ACEs), low (1-3 ACEs), moderate (4-6 ACEs), and high (>6 ACEs). Effects of ACEs on maternal DNAm (N = 240) were estimated using linear models. To evaluate evidence for intergenerational transmission, mediation analysis (N = 60 mother-child pairs) was used. Analysis of maternal samples displayed some shared but mostly distinct effects of ACEs on DNAm across low, moderate, and high ACEs categories. CLCN7 and PTPRN2 was associated with maternal DNAm in the low ACE group and this association replicated in the CHS. CLCN7 was also nominally significant in the gene expression correlation analysis among maternal profiles (N = 35), along with 11 other genes. ACE-associated methylation was observed in maternal and neonatal profiles in the COMT promoter region, with some evidence of mediation by maternal COMT methylation. Specific genomic loci exhibited mutually exclusive maternal ACE effects on DNAm in either maternal or neonatal population. There is some evidence for an intergenerational effect of ACEs, supported by shared DNAm signatures in the COMT gene across maternal-neonatal paired samples.

MeSH terms

Adult
Adverse Childhood Experiences*
Child
Chloride Channels
DNA Methylation
Female
Humans
Infant, Newborn
Leukocytes, Mononuclear
Mothers
Mouth Mucosa
Parents
Pregnancy

Substances

CLCN7 protein, human
Chloride Channels