Katherine King1, Susan Murphy2, Cathrine Hoyo3. 1. Environmental Public Health Division, U.S. Environmental Protection Agency, Chapel Hill, North Carolina, USA Department of Community and Family Medicine, Duke University Medical Center, Durham, North Carolina, USA. 2. Department of Obstetrics and Gynecology, Duke University, Durham, North Carolina, USA. 3. Department of Biological Sciences, North Carolina State University, Raleigh, North Carolina, USA.
Abstract
BACKGROUND: Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood. METHODS: We measured DNA methylation at DMRs regulating genomically imprinted domains (IGF2/H19, DLK1/MEG3, NNAT and PLAGL1) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010-2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences. RESULTS: Unadjusted race/ethnic differences only were evident for DMRs regulating MEG3 and IGF2; race/ethnic differences persisted in IGF2/H19 and NNAT after accounting for income and education. CONCLUSIONS: Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
BACKGROUND:Children born to parents with lower income and education are at risk for obesity and later-life risk of common chronic diseases, and epigenetics has been hypothesised to link these associations. However, epigenetic targets are unknown. We focus on a cluster of well-characterised genomically imprinted genes because their monoallelic expression is regulated by DNA methylation at differentially methylated regions (DMRs), are critical in fetal growth, and DNA methylation patterns at birth have been associated with increased risk of birth weight extremes and overweight status or obesity in early childhood. METHODS: We measured DNA methylation at DMRs regulating genomically imprinted domains (IGF2/H19, DLK1/MEG3, NNAT and PLAGL1) using umbilical cord blood leucocytes from 619 infants recruited in Durham, North Carolina in 2010-2011. We examined differences in DNA methylation levels by race/ethnicity of both parents, and the role that maternal socioeconomic status (SES) may play in the association between race/ethnic epigenetic differences. RESULTS: Unadjusted race/ethnic differences only were evident for DMRs regulating MEG3 and IGF2; race/ethnic differences persisted in IGF2/H19 and NNAT after accounting for income and education. CONCLUSIONS: Results suggest that parental factors may not only influence DNA methylation, but also do so in ways that vary by DMR. Findings support the hypothesis that epigenetics may link the observed lower SES during the prenatal period and poor outcomes such as low birth weight; lower birth weight has previously been associated with adult-onset chronic diseases and conditions that include cardiovascular diseases, diabetes, obesity and some cancers. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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Keywords:
GENETICS; PERINATAL EPIDEMIOLOGY; Social and life-course epidemiology
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