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Social disadvantage, genetic sensitivity, and children's telomere length
Open accessAbstract
Significance: This paper makes two contributions to research on the link between the social environment and health. Using data from a birth cohort study, we show that, among African American boys, those who grow up in highly disadvantaged environments have shorter telomeres (at age 9) than boys who grow up in highly advantaged environments. We also find that the association between the social environment and telomere length (TL) is moderated by genetic variation within the serotonin and dopamine pathways. Boys with the highest genetic sensitivity scores had the shortest TL when exposed to disadvantaged environments and the longest TL when exposed to advantaged environments. To our knowledge, this report is the first to document a gene–social environment interaction for TL, a biomarker of stress exposure.
Overview
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Written from the paper’s full text.
TL;DR
In 40 nine-year-old African American boys from the Fragile Families and Child Wellbeing Study, exposure to disadvantaged social environments was associated with shorter telomere length (TL), and this association was moderated by genetic variants in serotonergic and dopaminergic pathways. Boys with the highest genetic sensitivity scores had the shortest TL in disadvantaged environments and the longest TL in advantaged environments, consistent with differential susceptibility.
Key findings
- Living in a disadvantaged environment was associated with 19% shorter TL (P = 0.02).
- A doubling of the family income/needs ratio was associated with a 5% increase in TL (P = 0.03); compared with mothers with less than high school education, having a mother with a high school degree was associated with a 32% increase in TL (P = 0.006), and at least some postsecondary education was associated with a 35% increase (P = 0.005). Multiple family structure changes were associated with a 40% decline in TL (P = 0.010), and a low parenting quality score was associated with a 3% decrease.
- Serotonin sensitivity score interactions with the social environment were significant (M1: b = −0.22, P = 0.016; M2: b = −0.21, P = 0.049); dopamine interactions were less definitive (M3: b = −0.18, P = 0.098; M4: b = −0.07, P = 0.18).
- Saliva and blood leukocyte TL were highly correlated (R = 0.72, P = 0.002), although saliva TL was greater than blood leukocyte TL [6.5 kb ± 1.8 SD vs. 4.2 kb ± 1.2 SD, P < 0.001].
Methods
- Data came from the Fragile Families and Child Wellbeing Study; the analysis used 40 African American boys at age 9, selected from extreme environments: 20 from highly disadvantaged homes with maternal depression and 20 from advantaged homes without maternal depression.
- TL was measured from saliva DNA using a quantitative real-time PCR assay for absolute TL in kilobases per chromosome; environmental measures included economic conditions, parenting quality, family structure/stability, and maternal depression across five waves.
- Main analysis used robust ordinary least squares regression with Cook’s D and Huber weighting, plus gene-environment interaction models using serotonin and dopamine pathway genetic sensitivity scores.
Limitations
- The paper states that due to sample size limitations, it could not examine the independent effect of each environmental measure; pairwise tests showed SES measures were the strongest predictors of TL, while other coefficients declined dramatically when poverty ratio and mother’s education were included.
- Evident from the text: the sample is small (n = 40), restricted to African American boys, and selected for extreme environments, limiting power and generalizability.
- Evident from the text: TL was measured only at age 9, so the design cannot establish within-child changes in TL or causal direction, and the genetic sensitivity scores combine multiple variants with limited prior guidance on coding.
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A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, saliva and leukocyte DNA lengths were highly and significantly correlated (R = 0.72, P = 0.002) (Fig. S3).”
- Also stated in: § Abstract · boosted
“we use a saliva DNA source of TL, which we show to be highly correlated with blood leukocyte TL”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Sample.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Abstract · boosted
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“and having a mother with at least some postsecondary education is associated with a 35% increase in TL (P = 0.005).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“We report that exposure to disadvantaged environments is associated with reduced TL by age 9 y.”
- Also stated in: § Results · plain
“Model 1 (M1) of Table 2 shows that living in a disadvantaged environment was associated with a 19% shorter TL (P = 0.02).”
- Also stated in: § Discussion · plain
“Our analysis provides evidence that exposure to disadvantaged environments in childhood is associated with shorter TL.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes- Also stated in: § Results · plain
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“we tested the measured variables pairwise and found that the SES measures were the strongest predictors of TL.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Discussion
Strength:plain· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes? Load-bearing: unclear✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“model 4 shows that being exposed to multiple changes in family structure was associated with a 40% decline in a boy's TL (P = 0.010).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Results
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Fig. 1, Upper shows that, among children with 0 sensitizing serotonin genotypes, there is little difference in TL between children in advantaged and disadvantaged environments.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Gene-Environment Interactions with Telomere Length.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Although less definitive than in the case of the serotonergic pathway, the negative association between the social environment and TL is stronger for boys with dopaminergic pathway genetic variants most associated with higher levels environmental sensitivity (M3: b = -0.18,P value = 0.098; M4: b = -0.07,P value = 0.18).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Gene-Environment Interactions with Telomere Length.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“However, for children with higher levels of genetic sensitivity (i.e., those with 2+ sensitizing genotypes), we see a large difference.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Gene-Environment Interactions with Telomere Length.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“Telomere length was significantly greater in saliva than in blood leukocyte-derived DNA [6.5 kb ± 1.8 SD (saliva) vs. 4.2 kb ± 1.2 SD (peripheral mononuclear blood cells) P < 0.001] (Fig. S2).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Sample.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesA result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“whereas for boys with 1 and 2+ sensitizing dopamine genotypes, there is a large and significant difference by environment, with boys with sensitizing genotypes having the longer TL in advantaged environments and the shorter TL in disadvantaged environments.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Gene-Environment Interactions with Telomere Length.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passes
- It may state two separate claims as one. 3
- Probably not a substantial claim. 14
A result the paper reports from its own data — it cites no other source for it, so there is none to check. The quote shows it is in the paper.
In the paper
“the point estimates suggest that the most sensitive group has the longer TL in the advantaged environment and the shorter TL in the disadvantaged environment.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Gene-Environment Interactions with Telomere Length.
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesIt may state two separate claims as one.
In the paper
“Due to concerns of outliers and influential data points in a sample of 40, we use robust ordinary least squares (OLS) regression (using Cook's D and Huber weighting), which is 95% as efficient as traditional OLS (28).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Results
What the sources say
- Not checked yetcites [28]
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
None of the sources cited for this claim have been checked yet.
In the paper
“Disadvantaged social environments are associated with adverse health outcomes.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Abstract
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Body mass index (BMI) did not differ between harsh and nourishing environments.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Results
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Distribution of samples in the 96-well plates was randomized, and each plate contains at least 10 repeats from prior runs to detect and limit potential batch effects.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Sample.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim. It may state two separate claims as one.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“To mitigate batch effects, reference DNA from a tel-cell line and the same line after stable integration of tel were included in each plate.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Sample.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“Compared with the L allele, the S allele of the 5-HTTLPR polymorphism has been shown to be associated with reduced transcription (34).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Social Environment Measures.
What the sources say
- Not checked yetcites [34] source
Strength:boosted· not yet calibratedCausal:correlational· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Samples are measured in triplicate and the results are averaged.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Sample.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it. It may state two separate claims as one.
In the paper
“the Met allele of the Val158 Met polymorphism (rs4680) is known to decrease COMT activity (43).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Social Environment Measures.
What the sources say
- Not checked yetcites [43] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Telomere length was normalized by this reference to assure plate-to-plate consistency.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Sample.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“Due to sample size limitations, we were not able to examine the independent effect of each of these measures.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Discussion
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The models in Table 3 present estimates of the main and interaction effects of dopamine and serotonin pathway genes and the environmental factor for a boy's TL, controlling for age of the mother and age 9 standardized BMI.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Gene-Environment Interactions with Telomere Length.
Load-bearingStrength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
In the paper
“we focused on boys because prior research indicates that boys may be more sensitive than girls to negative family conditions (14).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Results
What the sources say
- Not checked yetcites [14] source
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
None of the sources cited for this claim have been checked yet.
In the paper
“A growing body of research shows that specific gene variants moderate the association between the social environment and children's health and well-being (13-15).”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Significance
What the sources say
Tests✓ Asserted: passes✓ Checkable: passes✓ Load-bearing: passes✓ Based: passesProbably not a substantial claim.
What the paper did — it cites no source for this, so there is none to check. The quote shows it is in the paper.
In the paper
“The coefficient of variation of a standard (DNA from a 40-y-old female) was 10% across ∼100, 96-well plates.”
§ Social disadvantage, genetic sensitivity, and children's telomere length > Sample.
Strength:plain· not yet calibratedTests✓ Asserted: passes✓ Checkable: passes✗ Load-bearing: fails✓ Based: passesProbably not a substantial claim. The paper’s conclusions may not depend on it.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“For example, recent data suggest that “high risk” genetic polymorphisms in the serotonin and dopamine systems may interact with early life adversity to affect adult LTL (Mitchell et al., 2014).”
From Psychiatric disorders and leukocyte telomere length: Underlying mechanisms linking mental illness with cellular aging (2015) · cites this paper as Mitchell et al., 2014
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Harsh parenting is called significant despite an unmarked estimate
MajorThe paper claims a significant association for harsh parenting, but its Table 2 coefficient has no significance marker, unlike estimates meeting the table's stated P < 0.05 threshold.
“In addition, we were able to document significant associations between family structure/stability and TL and harsh parenting and TL.”
“| Harsh parenting index | -0.03 |”
Education P values conflict with Table 2 significance markers
MinorThe reported P values of 0.006 and 0.005 do not meet the P < 0.001 threshold assigned to both education estimates by the table's double-asterisk marker.
“having a mother with a high school degree is associated with a 32% increase in a child's TL (P = 0.006), and having a mother with at least some postsecondary education is associated with a 35% increase in TL (P = 0.005).”
“| High school | 0.32** | | At least some college | 0.35** | | *P < 0.05, **P < 0.001, one-tailed. | |”
Education measure says four categories but lists three
MinorThe description announces four education categories but enumerates only three; Table 1 likewise displays three.
“To measure the mother's completed education, we used four categories:”
“(i) less than high school, (ii) high school graduate, and (iii) at least some college.”
Dopamine 2+ group is called significant and borderline
MinorThe results call the environmental difference significant for boys with 2+ sensitizing dopamine genotypes, whereas the figure description calls that group's P = 0.08 result borderline.
“for boys with 1 and 2+ sensitizing dopamine genotypes, there is a large and significant difference by environment”
“For the dopamine pathway genotypes, the environment difference is not significant for 0 genotypes (P = 0.63), significant for 1 genotype (P = 0.05), and borderline for 2+ genotypes (P = 0.08).”
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Self-citation
Metadata
- Authors
- Mitchell, C., Hobcraft, J., McLanahan, S. S., Siegel, S. R., Berg, A., Brooks-Gunn, J., Garfinkel, I., & Notterman, D.
- Affiliations
- University of Michigan (US)
- University of York (GB)
- Princeton University (US)
- Pennsylvania State University (US)
- Teachers College and the College of Physicians and Surgeons, Columbia University, New York, NY 10027;
- Columbia University (US)
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2014-04-07
- Volume
- 111
- Issue
- 16
- Pages
- 5944-5949
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC4000782
- OpenAlex
- W2120746465
- Semantic Scholar
- 66f55e89c17862e11c3ec313881d79ab792be518
- Cited by
- 281
- References
- 45
- Citations by year
- 2026: 3 · 2025: 27 · 2024: 7 · 2023: 17 · 2022: 15 · 2021: 12 · 2020: 22 · 2019: 36 · 2018: 23 · 2017: 38 · 2016: 37 · 2015: 30 · 2014: 12
- FWCI
- 26.00
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Pennsylvania
- Pennsylvania State University
- Penn State Clinical and Translational Science Institute
- National Institutes of Health (UL1TR000127, TL1TR000125)
- National Institute of Child Health and Human Development (R01 HD 36916, R01 HD 40421, R01HD39135)
- National Center for Advancing Translational Sciences (TL1 TR00012503)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD40421, R01-HD36916, R01 HD39135, R24HD047879, R01HD039135, R01HD36916, R01HD39135, and R01HD40421, R01HD076592, R24HD058486, R01HD036916, R01HD040421)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Telomeres, Telomerase, and Senescence
- Social Sciences › Health › Health disparities and outcomes
- Social Sciences › Psychology › Clinical Psychology › Child Abuse and Trauma
- Keywords
- telomere length, social deprivation, chronic stress, differential susceptibility hypothesis, genetic susceptibility, African American children, low income, maternal education, family structure, harsh parenting, serotonergic pathways, dopaminergic pathways, stress biomarkers, Fragile Families and Child Wellbeing Study
- MeSH terms
- Adult, Child, Dopamine, Humans, Male, Regression Analysis, Serotonin, Social Environment, Signal Transduction, Vulnerable Populations, Telomere Homeostasis, Gene-Environment Interaction
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