Socioeconomic changes predict genome-wide DNA methylation in childhood

Childhood socioeconomic position (SEP) is a major determinant of health and well-being across the entire life course. To effectively prevent and reduce health risks related to SEP, it is critical to better understand when and under what circumstances socioeconomic adversity shapes biological processes. DNA methylation (DNAm) is one such mechanism for how early life adversity "gets under the skin". Using data from a large, longitudinal birth cohort, we showed that changes in the socioeconomic environment may influence DNAm at age 7. We also showed that middle childhood (ages 6-7) may be a potential sensitive period when socioeconomic instability, reflected in parental job loss, is especially important in shaping DNAm. Our findings highlight the importance of socioeconomic stability during childhood, providing biological evidence in support of public programs to help children and families experiencing socioeconomic instability and other forms of socioeconomic adversity during childhood.

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GENOME-WIDE META-ANALYSIS SUPPORTS HETEROGENEITY IN POLYGENIC ARCHITECTURE OF DISABILITY

Innovation in Aging ◽

10.1093/geroni/igz038.335 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S87-S87

Author(s):

Alexander Kulminski ◽

Chansuk Kang ◽

Yury Loika ◽

Eric Stallard ◽

Irina Culminskaya

Keyword(s):

Molecular Mechanisms ◽

Meta Analysis ◽

Well Being ◽

Risk Scores ◽

Genome Wide ◽

Nominal Significance ◽

Individual Snps ◽

Replication Strategy ◽

Minor Alleles ◽

Using Data

Abstract Disability and frailty increase steeply with age after midlife. They comprise broad, non-specific aging-related health/well-being declines. Understanding the molecular mechanisms of these declines could help in combating processes related to intrinsic aging. We performed genome-wide meta-analysis of disability using data on N=12,550 disabled individuals of Caucasian ancestry from five independent studies with N=24,068 genotyped participants. Disability was measured using the Activities of Daily Living (ADL) scale. A subject was considered disabled if he/she had at least one ADL impairment. All subjects in our study were aged 50+ years. The analysis followed a discovery-replication strategy using two studies as discovery samples and three others as replication samples. At the discovery stage, we selected SNPs at nominal significance (p<0.05) and evaluated their associations with disability in the replication samples. Meta-analysis across all studies identified 30 SNPs (24 loci) at p<10e-4. SNPs from four loci (chromosomes 2, 8, and 12) attained suggestive significances at p<10-5. We constructed two polygenic risk scores (PGRS) using these 30 SNPs whose minor alleles were positively (19 SNPs) and negatively (11 SNPs) associated with disability, PGRS_p and PGRS_n, respectively. Meta-analysis across all studies identified strong effects for PGRS_p (beta=0.436, p=1.18×10e-32) and PGRS_n (beta=-0.426, p=8.74×10e-19). The associations for the PGRSs observed in two discovery studies were replicated in three independent studies. The lack of genome-wide significant effects of individual SNPs combined with the highly significant effects of the PGRSs shows that, in line with the heterogeneous origin of disability, its genetic architecture is of highly heterogeneous polygenic origin.

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Early life adversity as a predictor of sense of purpose during adulthood

International Journal of Behavioral Development ◽

10.1177/0165025416681537 ◽

2016 ◽

Vol 42 (1) ◽

pp. 143-147 ◽

Cited By ~ 9

Author(s):

Patrick L. Hill ◽

Nicholas A. Turiano ◽

Anthony L. Burrow

Keyword(s):

Early Life ◽

Life Experiences ◽

Well Being ◽

The United States ◽

Chronological Age ◽

Early Life Adversity ◽

Positive Aging ◽

Sense Of Purpose ◽

Potential Factors ◽

Using Data

Feeling a sense of purpose in life appears to hold consistent benefits for positive aging and well-being. As such, it is important to consider the potential factors that promote or hinder the development of purposefulness over the lifespan. For instance, it remains unclear whether early life experiences, particularly adverse ones, may hold lasting influences on whether one feels purposeful into adulthood. The current study examined whether early life adversity predicted a diminished sense of purpose in adulthood using data from participants ( N = 3835) in the Midlife in the United States (MIDUS) study. Reports of early life adversity were associated with lower levels of purpose in adulthood, and chronological age failed to moderate this relationship.

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Use of Two Complementary Bioinformatic Approaches to Identify Differentially Methylated Regions in Neonatal Sepsis

The Open Bioinformatics Journal ◽

10.2174/1875036202114010144 ◽

2021 ◽

Vol 14 (1) ◽

pp. 144-152

Author(s):

Paula Navarrete ◽

María José Garzón ◽

Sheila Lorente-Pozo ◽

Salvador Mena-Mollá ◽

Máximo Vento ◽

...

Keyword(s):

Dna Methylation ◽

Neonatal Sepsis ◽

Late Onset ◽

Underlying Disease ◽

Methylation Pattern ◽

Differentially Methylated Regions ◽

Genome Wide ◽

Bioinformatic Approaches ◽

Using Data ◽

Underlying Mechanisms

Background: Neonatal sepsis is a heterogeneous condition affecting preterm infants whose underlying mechanisms remain unknown. The analysis of changes in the DNA methylation pattern can contribute to improving the understanding of molecular pathways underlying disease pathophysiology. Methylation EPIC 850K BeadChip technology is an excellent tool for genome-wide methylation analyses and the detection of differentially methylated regions (DMRs). Objective: The aim is to identify DNA methylation traits in complex diseases, such as neonatal sepsis, using data from Methylation EPIC 850K BeadChip arrays. Methods: Two different bioinformatic methods, DMRcate (a supervised approach) and mCSEA (an unsupervised approach), were used to identify DMRs using EPIC data from leukocytes of neonatal septic patients. Here, we describe with detail the implementation of both methods as well as their applicability, briefly discussing the results obtained for neonatal sepsis. Results: Differences in methylation levels were observed in neonatal sepsis patients. Moreover, differences were identified between the two subsets of the disease: Early-Onset neonatal Sepsis (EOS) and Late-Onset Neonatal Sepsis (LOS). Conclusion: This approach by using DMRcate and mCSA helped us to gain insight into the intricate mechanisms that may drive EOS and LOS development and progression in newborns.

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Identification of loci where DNA methylation potentially mediates genetic risk of type 1 diabetes

10.1101/248260 ◽

2018 ◽

Author(s):

Jody Ye ◽

Tom G Richardson ◽

Wendy L McArdle ◽

Caroline L Relton ◽

Kathleen M Gillespie ◽

...

Keyword(s):

Dna Methylation ◽

Type 1 Diabetes ◽

Autoimmune Diabetes ◽

Epigenetic Mechanism ◽

Childhood And Adolescence ◽

Nucleotide Polymorphisms ◽

Genome Wide ◽

Causal Pathway ◽

Using Data

AbstractThe risk of Type 1 Diabetes (T1D) comprises both genetic and environmental components. We investigated whether genetic susceptibility to T1D could be mediated by changes in DNA methylation, an epigenetic mechanism that potentially plays a role in autoimmune diabetes. Using data from a non-diabetic population comprising blood samples taken at birth (n=844), childhood (n=911) and adolescence (n=907), we evaluated the associations between 65 top GWAS single nucleotide polymorphisms (SNPs) and genome-wide DNA methylation levels. We identified 159 proximal SNP-cytosine phosphate guanine (CpG) pairs (cis), and 7 distal SNP-CpG associations (trans) at birth, childhood, and adolescence. There was also a systematic enrichment for methylation related SNPs to be associated with T1D across the genome, after controlling for genomic characteristics of the SNPs, implying that methylation could either be on the causal pathway to T1D or a non-causal biomarker. Combining the principles of Mendelian Randomization and genetic colocalization analysis, we provided evidence that at 5 loci,ITGB3BP,AFF3,PTPN2,CTSHandCTLA4, DNA methylation is potentially on the causal pathway to T1D.

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Sensitive periods for the effect of childhood adversity on DNA methylation: Results from a prospective, longitudinal study

10.1101/271122 ◽

2018 ◽

Cited By ~ 1

Author(s):

Erin C. Dunn ◽

Thomas W. Soare ◽

Andrew J. Simpkin ◽

Matthew J. Suderman ◽

Yiwen Zhu ◽

...

Keyword(s):

Dna Methylation ◽

Longitudinal Study ◽

Early Life ◽

Multiple Testing ◽

Sensitive Period ◽

Multiple Testing Correction ◽

Early Life Adversity ◽

Prospective Longitudinal Study ◽

Sensitive Periods ◽

Prospective Longitudinal

AbstractBackgroundExposure to “early life” adversity is known to predict DNA methylation (DNAm) patterns that may be related to prolonged psychiatric risk. However, few studies have investigated whether adversity has time-dependent effects based on the age at exposure.MethodsUsing a two-stage structured life course modeling approach (SLCMA), we tested the hypothesis that there are sensitive periods when adversity induced greater DNAm changes. We tested this hypothesis in relation to two alternative explanations: an accumulation hypothesis, in which the effect of adversity on DNAm increases with the number of occasions exposed, regardless of timing, and a recency model, in which the effect of adversity is stronger for more proximal events. Data came from the Accessible Resource for Integrated Epigenomics Studies (ARIES), a subsample of mother-child pairs from the Avon Longitudinal Study of Parents and Children (ALSPAC; n=670-776).ResultsAfter covariate adjustment and multiple testing correction, we identified 40 CpG sites that were differentially methylated at age 7 following exposure to adversity. Most loci (n=32) were predicted by the timing of adversity, namely exposures during infancy. Neither the accumulation nor recency of the adversity explained considerable variability in DNAm. A standard EWAS of lifetime exposure (vs. no exposure) failed to detect these associations.ConclusionsThe developmental timing of adversity explains more variability in DNAm than the accumulation or recency of exposure. Infancy appears to be a sensitive period when exposure to adversity predicts differential DNAm patterns. Classification of individuals as exposed vs. unexposed to “early life” adversity may dilute observed effects.

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Parental belief in ‘healthy risk’ lead to fewer child accidents and injuries: fact or fiction?

International Journal for Population Data Science ◽

10.23889/ijpds.v3i2.514 ◽

2018 ◽

Vol 3 (2) ◽

Author(s):

Louise Marryat ◽

John Frank

Keyword(s):

Middle Childhood ◽

Child Outcomes ◽

Well Being ◽

Parental Perceptions ◽

Birth Cohort Study ◽

Hospital Data ◽

Perceptions Of Risk ◽

Health And Wellbeing ◽

Using Data ◽

Parental Belief

There has been a substantial amount of debate around the role of parental risk aversity in children's health and wellbeing, with results suggesting that, whilst in the short-term, parents may ensure their children's safety, in the longer-term, children's psychological well-being may be compromised, and a lack of activity may result in a range of other poorer outcomes (Little and Wyver, 2008). Whilst some approaches to risk can be seen as extreme, there appears to be a role for healthy, positive risk in parenting (Bundy et al., 2009). Studies to date in this area have mostly comprised a mixture of survey and observational data, with little evidence on the relationship between parental risk aversity and child outcomes, such as accidents and injuries. The current study explores these associations, using data exploring parental perceptions of risk, taken at ages 3 and 5, from the Growing Up in Scotland birth cohort study, linked with administrative hospital data about child accidents and injuries up to age 11. This paper will investigate results on associations between parental perceptions of risk, and child accidents and injuries, as well as exploring whether these impacts change through early to middle childhood, and whether they differ by socio-economic classification.

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Examining the epigenetic mechanisms of childhood adversity and sensitive periods: a gene set-based approach

10.1101/2021.06.22.21259356 ◽

2021 ◽

Author(s):

Yiwen Zhu ◽

Alexandre A Lussier ◽

Andrew D.A.C. Smith ◽

Andrew J. Simpkin ◽

Matthew J. Suderman ◽

...

Keyword(s):

Middle Childhood ◽

Developmental Plasticity ◽

Childhood Adversity ◽

Sensitivity Analyses ◽

Sensitive Period ◽

Epigenetic Mechanisms ◽

Early Life Adversity ◽

Linear Discriminant ◽

Gene Set ◽

Sensitive Periods

Background: Sensitive periods are developmental stages of heightened plasticity when exposure to childhood adversity may exert lasting impacts. A few biological pathways are known to play key roles in regulating sensitive period plasticity across brain development. Epigenetic mechanisms including DNA methylation (DNAm) may provide a means through which life experiences during sensitive periods induce long-term biological changes. In the current study, we investigated the possibility that adversity during sensitive periods led to DNAm changes in genes that regulate the timing and duration of sensitive periods in development. Methods: Using childhood adversity data and genome-wide DNAm profiles from the Avon Longitudinal Study of Parents and Children (n=785), we summarized DNAm variation of CpG sites in the promoters of genes regulating sensitive periods with the first two principal components (PCs). DNAm summaries were calculated for genes regulating sensitive period opening (ngenes=15), closing (ngenes=36), and expression/duration (ngenes=8). We then performed linear discriminant analysis to test associations between these DNAm summaries and the timing of exposure to seven types of adversity. Results: Sexual or physical abuse and financial hardship during middle childhood (6-7 years) were associated with DNAm of genes regulating the onset and duration of sensitive periods. Sensitivity analyses assessing the presence of any exposure before age 7 and a composite measure of adversity yielded fewer signals, highlighting the importance of accounting for timing and adversity type. Conclusions: With our novel gene set-based approach, we have uncovered suggestive evidence that epigenetic regulation of developmental plasticity may be affected by early life adversity. The complementarity of our gene-level view of the epigenome to the more common and granular epigenome-wide association study may yield novel mechanistic insights not only for adversity but also for other exposures and outcomes.

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