Epigenome-wide meta-analysis of blood DNA methylation in newborns and children identifies numerous loci related to gestational age

Background Preterm birth and shorter duration of pregnancy are associated with increased morbidity in neonatal and later life. As the epigenome is known to have an important role during fetal development, we investigated associations between gestational age and blood DNA methylation in children. Methods We performed meta-analysis of Illumina's HumanMethylation450-array associations between gestational age and cord blood DNA methylation in 3648 newborns from 17 cohorts without common pregnancy complications, induced delivery or caesarean section. We also explored associations of gestational age with DNA methylation measured at 4-18 years in additional pediatric cohorts. Follow-up analyses of DNA methylation and gene expression correlations were performed in cord blood. DNA methylation profiles were also explored in tissues relevant for gestational age health effects: fetal brain and lung. Results We identified 8899 CpGs in cord blood that were associated with gestational age (range 27-42 weeks), at Bonferroni significance, P <1.06 x 10(- 7), of which 3343 were novel. These were annotated to 4966 genes. After restricting findings to at least three significant adjacent CpGs, we identified 1276 CpGs annotated to 325 genes. Results were generally consistent when analyses were restricted to term births. Cord blood findings tended not to persist into childhood and adolescence. Pathway analyses identified enrichment for biological processes critical to embryonic development. Follow-up of identified genes showed correlations between gestational age and DNA methylation levels in fetal brain and lung tissue, as well as correlation with expression levels. Conclusions We identified numerous CpGs differentially methylated in relation to gestational age at birth that appear to reflect fetal developmental processes across tissues. These findings may contribute to understanding mechanisms linking gestational age to health effects.Peer reviewe

A trickle or a torrent? Understanding the extent of summer “melt” among college-intending high school graduates. Social Science Quarterly. doi:10.1111/ssqu.12032

Objectives. The object of this study was to examine whether college-intending, low-income high school graduates are particularly susceptible to having their postsecondary education plans change, or even fall apart, during the summer after high school graduation. College access research has largely overlooked this time period. Yet, previous research indicates that a sizeable share of low-income students who had paid college deposits reconsidered where, and even whether, to enroll in the months following graduation. We assess the extent to which this phenomenon-commonly referred to as &quot;summer melt&quot;-is broadly generalizable. Methods. We employ two data sources, a national survey and administrative data from a large metropolitan area, and regression analysis to estimate the prevalence of summer melt. Results. Our analyses reveal summer melt rates of sizeable magnitude: ranging from 8 to 40 percent. Conclusions. Our results indicate that low-income, college-intending students experience high rates of summer attrition from the college pipeline. Given the goal of improving the flow of low-income students to and through college, it is imperative to investigate how to effectively intervene and mitigate summer melt. The share of students enrolling in higher education in the United States has increased steadily in recent decades. Nevertheless, enrollment rates of low-income youth continue to lag behind those of their wealthier peers. Research seeking to explain these persistent-and widening-gaps has focused predominantly on student characteristics, academic preparation, and access to * Direct correspondence to Benjamin L. Castleman (now at the University of Virginia), Curry School of Education, The University of Virginia, P.O. Box 400265, Charlottesville, VA 22904 [email protected] or Lindsay C. Page, Center for Education Policy Research, Harvard University, 50 Church, Cambridge, MA 02138 [email protected] . We will share all coding and all data from uAspire for replication purposes. We are unable to provide restricted-use ELS:2002 data. We gratefully acknowledge uAspire for providing us data on applicants to their Last Dollar Scholarship program and further acknowledge Bob GianninoRacine, Erin Cox, and Claire Dennison at uAspire for their collaborative partnership in this project. We are grateful to Christopher Avery and Bridget Terry Long for their support and guidance and to Richard Murnane for providing feedback on previous versions of this article. Finally, we acknowledge Karen Arnold, whose research and guidance led us to further examine the prevalence of summer-specific barriers to college access

Longitudinal associations of DNA methylation and sleep in children: a meta-analysis

Abstract Background Sleep is important for healthy functioning in children. Numerous genetic and environmental factors, from conception onwards, may influence this phenotype. Epigenetic mechanisms such as DNA methylation have been proposed to underlie variation in sleep or may be an early-life marker of sleep disturbances. We examined if DNA methylation at birth or in school age is associated with parent-reported and actigraphy-estimated sleep outcomes in children. Methods We meta-analysed epigenome-wide association study results. DNA methylation was measured from cord blood at birth in 11 cohorts and from peripheral blood in children (4–13 years) in 8 cohorts. Outcomes included parent-reported sleep duration, sleep initiation and fragmentation problems, and actigraphy-estimated sleep duration, sleep onset latency and wake-after-sleep-onset duration. Results We found no associations between DNA methylation at birth and parent-reported sleep duration (n = 3658), initiation problems (n = 2504), or fragmentation (n = 1681) (p values above cut-off 4.0 × 10–8). Lower methylation at cg24815001 and cg02753354 at birth was associated with longer actigraphy-estimated sleep duration (p = 3.31 × 10–8, n = 577) and sleep onset latency (p = 8.8 × 10–9, n = 580), respectively. DNA methylation in childhood was not cross-sectionally associated with any sleep outcomes (n = 716–2539). Conclusion DNA methylation, at birth or in childhood, was not associated with parent-reported sleep. Associations observed with objectively measured sleep outcomes could be studied further if additional data sets become available