Maternal Smoking During Pregnancy Association with DNA Methylation: A Sibling Comparison Design
Abstract
Maternal smoking during pregnancy (MSDP) is still occurring in the United States, as of 2021, at an average rate of 6% (CDC, WONDER). This proximal exposure to MSDP has been associated with decreased fetal head size, increased risk of SIDS, and increased risk for low birthweight (Abraham et al., 2017, Avsar et al., 2021; Knopik et al., 2016b) in infants exposed to MSDP compared to infants not exposed to MSDP. Additionally, MSDP has been associated with epigenetics in the form of differential DNA methylation (DNAm) in children and adolescents who were exposed to MSDP. Among these studies, there has been consistency in gene-specific findings of differential methylation in global DNAm (across the genome), AHRR, CYP1A1, CNTNAP2, MYOIG, and GFI1 (Ladd-Acosta et al., 2015; Lee et al., 2015; Richmond et al., 2015; Rzehak et al., 2016). Using the frameworks of the Developmental Origins of Health and Disease, as well as Ecological Systems Theory, the current study aims to (1) test the effect of MSDP on global DNAm (across the genome) cross-sectionally in 8-17 y/o children and adolescents, (2) attempt to replicate and analyze the MSDP impacts on AHRR, CYP1A1, CNTNAP2, MYOIG, and GFI1, and (3) adjust for several prenatal and postnatal covariates (second-hand smoke and particulate matter (PM2.5), specifically) in an attempt to isolate the MSDP exposure on DNAm analysis. In a sample of 325 8-17 y/o children whose sibling was exposed to more or less MSDP compared to them, it was found that higher child-specific MSDP was associated with more global methylation and less CNTNAP2 methylation, possibly suggesting evidence for a partially causal pathway between MSDP and DNAm for these genetic outcomes. Both child-specific and family-average MSDP were associated with CYP1A1 and MYO1Gmethylation. There were also various findings related to child sex and age covariates, as well as postnatal PM2.5. Future studies focused on replication of these findings in a longitudinal genetic design could further confirm the associations found in the current study.
Degree
M.S.
Advisors
Marceau, Purdue University.
Subject Area
Atmospheric Chemistry|Atmospheric sciences|Biochemistry|Genetics|Obstetrics and gynecology|Public health
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