Poster No:
2190
Submission Type:
Abstract Submission
Authors:
Ryan Tung1, Carly O'Neill1, Felicia Hardi1, Leigh Goetschius1, Dan Notterman2, Luke Hyde1, Christopher Monk1, Colter Mitchell1
Institutions:
1University of Michigan, Ann Arbor, MI, 2Princeton University, Princeton, NJ
First Author:
Ryan Tung
University of Michigan
Ann Arbor, MI
Co-Author(s):
Luke Hyde
University of Michigan
Ann Arbor, MI
Introduction:
Lead is a neurotoxic substance that has been shown to significantly affect the developing
brain through multiple mechanisms. Lead exposure can have broad, long-lasting effects on a
variety of physiological processes including epigenetic modification and myelination. Early
exposure to lead can occur in-utero leaving an epigenetic signature of exposure and posing
lasting health issues. The relationship between epigenetics and in-utero lead exposure may
provide insight into the molecular mechanisms of lead's toxic effects and serve as a proxy of
measured in-utero lead exposure.
Methods:
181 adolescents from the Study in Adolescent Neural Development (SAND) were included in the analyses. SAND is a subset of participants from the Future of Families and Child Wellbeing Study, a population-based longitudinal cohort study with substantial representation of marginalized youths. Participants provided DNA methylation (DNAm) via saliva samples at ages 9 and 15 as well as diffusion MRI scans at 15. DNAm scores of prenatal lead exposure in umbilical cord blood were quantified using weights derived by (Wu et al., 2017) and applied to age 9 and 15 DNAm samples, which were then residualized for known confounders (immune cell and fibroblast proportion, batch, and maternal smoking at birth). Diffusion MRI was processed using the MRtrix pipeline that generated 94x94 individualized matrices representing whole-brain structural connectivity connectomes. Graph analysis was then applied to the resulting matrices to generate metrics of network architecture: global efficiency, modularity, and transitivity. All measures were z-score standardized. All analyses controlled for participant age, gender, birth city, race, mother's education at birth, poverty ratio at birth, and current poverty ratio. All results are corrected with false discovery rate correction.
Results:
A higher prenatal DNA methylation lead score measured at age 9 was associated with decreased structural global network efficiency (β = -0.185, q = .025). No association was found between prenatal lead score and modularity or transitivity using methylation measured at 9 or all three brain metrics at 15.
Conclusions:
The present findings suggest that greater prenatal DNAm scores of lead derived from children at age 9 may contribute to differences in white matter connectivity organization across development. Lack of an association between prenatal DNAm scores of lead at age 15 and brain metrics may reflect a decay in lead methylation signal between 9 and 15, possibly as a result of in utero and early life lead exposures being deposited in bone rather than immune cells. Future analyses will investigate the impact of lead scores on subnetworks.
Genetics:
Genetics Other
Lifespan Development:
Early life, Adolescence, Aging 2
Modeling and Analysis Methods:
Diffusion MRI Modeling and Analysis
Neuroanatomy, Physiology, Metabolism and Neurotransmission:
White Matter Anatomy, Fiber Pathways and Connectivity 1
Keywords:
Development
Toxins
WHITE MATTER IMAGING - DTI, HARDI, DSI, ETC
1|2Indicates the priority used for review
Provide references using author date format
Wu S, Hivert M-F, Cardenas A, Zhong J, Rifas-Shiman SL, Agha G, Colicino E, Just AC, Amarasiriwardena C,
Lin X, Litonjua AA, DeMeo DL, Gillman MW, Wright RO, Oken E, Baccarelli AA (2017) Exposure to Low Levels of Lead in Utero and Umbilical Cord 41 Blood DNA Methylation in Project Viva: An Epigenome Wide Association Study. Environ Health Perspect 125:087019.