Differentially methylated regions and methylation QTLs for teen depression and early puberty in the Fragile Families Child Wellbeing Study

Abstract

The Fragile Families Child Wellbeing Study (FFCWS) is a longitudinal cohort of ethnically diverse and primarily low socioeconomic status children and their families in the U.S. Here, we analyze DNA methylation data collected from 748 FFCWS participants in two waves of this study, corresponding to participant ages 9 and 15. Our primary goal is to leverage the DNA methylation data from these two time points to study methylation associated with two key traits in adolescent health that are over-represented in these data: Early puberty and teen depression. We first identify differentially methylated regions (DMRs) for depression and early puberty. We then identify DMRs for the interaction effects between these two conditions and age by including interaction terms in our regression models to understand how age-related changes in methylation are influenced by depression or early puberty. Next, we identify methylation quantitative trait loci (meQTLs) using genotype data from the participants. We also identify meQTLs with epistatic effects with depression and early puberty. We find enrichment of our interaction meQTLs with functional categories of the genome that contribute to the heritability of co-morbid complex diseases. We replicate our meQTLs in data from the GoDMC study. This work leverages the important focus of the FFCWS data on disadvantaged children to shed light on the methylation states associated with teen depression and early puberty, and on how genetic regulation of methylation is affected in adolescents with these two conditions.

Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma

“…Previous genomic studies have focused on exploring DNA methylation changes between pre-and post-puberty [24][25][26][27][28] in peripheral blood immune cells. Yet, despite the clear evidence of epigenetic reprogramming during pubertal development, gene expression changes throughout puberty remain understudied.…”

“…While the epigenetic changes accompanying pubertal development have been explored previously in several studies [24][25][26][27][28] , the likely subsequent transcriptional changes are largely unknown. We explored the gene expression changes in males and females tracked longitudinally through puberty.…”

“…The molecular mechanisms underlying the physiological and pathological changes in the immune system during puberty remain understudied and largely uncharacterized. Previous studies have explored the effects of puberty on DNA methylation [23][24][25][26][27][28] in peripheral blood immune cells. DNA methylation is an important epigenetic mark regulating gene expression during development and aging 29 .…”

Analysis of transcriptional changes in the immune system associated with pubertal development in a longitudinal cohort of children with asthma

“…Previous genomic studies have focused on exploring DNA methylation changes between pre-and postpuberty [24][25][26][27][28] in peripheral blood immune cells. Yet, despite the clear evidence of epigenetic reprogramming during pubertal development, gene expression changes throughout puberty remain understudied.…”

“…The molecular mechanisms underlying the physiological and pathological changes in the immune system during puberty remain understudied and largely uncharacterized. Previous studies have explored the effects of puberty on DNA methylation [21][22][23][24][25][26] in peripheral blood immune cells. DNA methylation is an important epigenetic mark regulating gene expression during development and aging 27 .…”