Socioeconomic Changes Predict Genome-wide DNA Methylation in Childhood
Key findings
- Alterations in DNA methylation (DNAm) have been proposed as the mechanism by which children from families of low socioeconomic position (SEP) have greater risk of short- and long-term health deficits than children from families of high SEP
- Experiencing a change in the socioeconomic environment explained, on average, a 3.2% difference in DNAm levels, and across six SEP indicators analyzed, the majority of loci (17 of 62) detected were related to neighborhood disadvantage
- Middle childhood (ages 6-7) seemed to be a potential sensitive period when socioeconomic instability, reflected in parental job loss, was especially important in shaping DNAm
- If future studies show DNAm alterations are harmful to health, rather than adaptive, programs designed to promote socioeconomic stability for children should consider interventions at both the household and neighborhood levels
It's been established that children growing up in families of low socioeconomic position (SEP) have greater risk of short- and long-term deficits in physical, mental and behavioral health than children from families of high SEP.
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Numerous studies have focused on DNA methylation (DNAm) as the biological mechanism that might underlie these effects of SEP. Alterations in DNAm don't alter the sequence of the genome, but they have "epigenetic" effects—they influence how genes are expressed.
Erin C. Dunn, ScD, MPH, an investigator in the Psychiatric and Neurodevelopmental Genetics Unit and the Center for Genomic Medicine at Massachusetts General Hospital, Jiaxuan Liu, PhD, former research fellow in the Dunn Lab, and colleagues conducted the first study of the relationship between SEP and DNAm in which DNAm was measured during childhood. They report in Human Molecular Genetics that certain changes in the socioeconomic environment, particularly in middle childhood, alter epigenetic patterns at least in the short term.
Methods
The team retrospectively analyzed data on 946 singleton offspring in ARIES, a subsample of the Avon Longitudinal Study of Parents and Children in the United Kingdom. Via maternal report through mailed questionnaires, the researchers tracked six indicators of SEP: low family income, job loss, income reduction, financial hardship, major financial problems and neighborhood disadvantage.
Each indicator was measured repeatedly during three developmental time periods: very early childhood (0–2 years of age), early childhood (3–5 years), and middle childhood (6–7 years). DNAm was measured from blood at age 7.
Childhood SEP and Variance in DNAm
DNAm occurs when methyl groups are added to cytosines in the DNA sequence, typically within cytosine–guanine (CpG) dinucleotides. The researchers identified 62 CpGs where exposure to socioeconomic adversity explained more than 3% variance in DNAm.
Most of the 62 CpGs were linked to neighborhood disadvantage (17 loci) or job loss (15). The other 30 were associated with low family income (13 loci), financial hardship (nine), major financial problem (five), or income reduction (three).
Absolute effect estimates ranged from 0.1% to 12.8%, and on average, exposure to socioeconomic adversity was associated with a 3.2% difference in DNAm levels. Socioeconomic adversity explained 3.3% of the variance in DNAm across CpG sites after controlling for covariates.
Life Course Hypotheses
This was also the first study to simultaneously test three hypotheses about time-dependent effects of socioeconomic adversity on DNAm. They found:
- The accumulation hypothesis assumes the impact of low SEP on DNAm increases with the number of time periods of exposure
- The sensitive period hypothesis assumes the impact is greater during a certain developmental period
- The mobility hypothesis assumes the impact is driven by improvement or worsening of SEP between adjacent developmental time periods
All three hypotheses were tested for low family income, financial hardship, major financial problems and neighborhood disadvantage. 44 CpGs were identified, with the majority related to sensitive period (22 loci) or mobility (worsening SEP, 20 loci).
Specifically, sensitive period was selected for all nine CpGs identified from financial hardship, with middle childhood selected for eight of them. Mobility explained more DNAm variability resulting from neighborhood disadvantage (11 of 17 loci) and major financial problems (four of five loci).
Only the accumulation and sensitive period hypotheses were tested for job loss and income reduction, since these indicators inherently reflect change. The strongest evidence was again for sensitive period effects, with middle childhood most selected for job loss and very early childhood most selected for income reduction.
Implications for Public Health
A major unanswered question is whether DNAm changes in the face of socioeconomic adversity reflect increased resilience, risk or both. If future studies show DNAm alterations are harmful to health:
- Children and families might benefit from policies and social programs aimed at minimizing socioeconomic instability, especially for lower-income families who may lack a safety net to draw from during times of transition such as job loss
- Programs designed to promote socioeconomic stability for children should consider interventions at the household level (e.g., promoting supportive parenting styles or social cohesion during times of instability and/or heightened parental stress) and neighborhood level (e.g., after-school programs and community recreational centers)
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