Evidence map›Paper›PMID 25580720›Full record

ArticleEpigenetics2015

Quality control and statistical modeling for environmental epigenetics: a study on in utero lead exposure and DNA methylation at birth.

Jaclyn M Goodrich, Brisa N Sánchez, Dana C Dolinoy, Zhenzhen Zhang, Mauricio Hernández-Ávila, Howard Hu, Karen E Peterson, Martha M Téllez-Rojo

Open access · bronzeAbstract read
In one paragraph

Article in Epigenetics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
30citing papers in PubMed, 1 pooled it
3.2field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

30 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Increased risk of severe neonatal opioid withdrawal syndrome in pregnancies with low placental ABCB1 DNA methylation.Journal of perinatology : official journal of the California Perinatal Association · 2025
    Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Neonatal Lead (Pb) Exposure and DNA Methylation Profiles in Dried Bloodspots.International journal of environmental research and public health · 2020
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Article
  19. Review
  20. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 7 institutions in 4 countries.

Jaclyn M Goodricha Department of Environmental Health Sciences ; University of Michigan School of Public Health ; Ann Arbor , MI USA.
Brisa N Sánchez
Dana C Dolinoy
Zhenzhen Zhang
Mauricio Hernández-Ávila
Howard Hu
Karen E Peterson
Martha M Téllez-Rojo
University of Michigan–Ann Arbor · US3M (United States) · USAnn Arbor Center for Independent Living · USHarvard University · USInstituto Nacional de Salud Pública · MXMichigan United · USNational Institute of Public Health · SI

Funding

Michigan Institute for Clinical and Health Research (MCHR)UL1TR000433 · NCATS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI MASHOUR, GEORGE ALEXANDER · 2012 to 2016
$49.9M
Strategic Vision & Impact on Environmental HealthP30ES017885 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI AMY J SCHULZ · 2011 to 2026
$21.3M
VANADIUM AND HUMAN HEALTHP42ES005947 · NIEHS · HARVARD UNIVERSITY (SCH OF PUBLIC HLTH) · PI KELSEY, KARL TIMOTHY · 1992 to 2006
$19.6M
Stress, Lead, Iron Deficiency and NeurodevelopmentR01ES013744 · NIEHS · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI Robert O Wright · 2007 to 2026
$13.4M
LEAD DOSE BIOMARKERS, REPRODUCTION, AND INFANT OUTCOMESR01ES007821 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PETERSON, KAREN EILEEN · 1998 to 2010
$4.7M
Project 3: Developmental Exposures and Diet: Epigenetics of Metabolic SyndromeP01ES022844 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PADMANABHAN, VASANTHA, PETERSON, KAREN EILEEN · 2013 to 2018
$3.9M
Metal Mixtures and NeurodevelopmentR01ES014930 · NIEHS · BRIGHAM AND WOMEN'S HOSPITAL · PI WRIGHT, ROBERT O · 2006 to 2010
$3.2M
Project 1: Prenatal Lead Exposure, Early Childhood Growth, and Sexual MaturationP20ES018171 · NIEHS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PETERSON, KAREN EILEEN · 2010 to 2012
$584k
NCATS NIH HHS 2UL1TR00433NCATS NIH HHS UL1 TR000433NIEHS NIH HHS P01 ES022844NIEHS NIH HHS P01 ES02284401NIEHS NIH HHS P20 ES018171NIEHS NIH HHS P30 ES017885NIEHS NIH HHS P42 ES005947NIEHS NIH HHS P42 ES05947NIEHS NIH HHS R01 ES007821NIEHS NIH HHS R01 ES013744NIEHS NIH HHS R01 ES014930
6 · The paper itself

Abstract

DNA methylation data assayed using pyrosequencing techniques are increasingly being used in human cohort studies to investigate associations between epigenetic modifications at candidate genes and exposures to environmental toxicants and to examine environmentally-induced epigenetic alterations as a mechanism underlying observed toxicant-health outcome associations. For instance, in utero lead (Pb) exposure is a neurodevelopmental toxicant of global concern that has also been linked to altered growth in human epidemiological cohorts; a potential mechanism of this association is through alteration of DNA methylation (e.g., at growth-related genes). However, because the associations between toxicants and DNA methylation might be weak, using appropriate quality control and statistical methods is important to increase reliability and power of such studies. Using a simulation study, we compared potential approaches to estimate toxicant-DNA methylation associations that varied by how methylation data were analyzed (repeated measures vs. averaging all CpG sites) and by method to adjust for batch effects (batch controls vs. random effects). We demonstrate that correcting for batch effects using plate controls yields unbiased associations, and that explicitly modeling the CpG site-specific variances and correlations among CpG sites increases statistical power. Using the recommended approaches, we examined the association between DNA methylation (in LINE-1 and growth related genes IGF2, H19 and HSD11B2) and 3 biomarkers of Pb exposure (Pb concentrations in umbilical cord blood, maternal tibia, and maternal patella), among mother-infant pairs of the Early Life Exposures in Mexico to Environmental Toxicants (ELEMENT) cohort (n = 247). Those with 10 μg/g higher patella Pb had, on average, 0.61% higher IGF2 methylation (P = 0.05). Sex-specific trends between Pb and DNA methylation (P < 0.1) were observed among girls including a 0.23% increase in HSD11B2 methylation with 10 μg/g higher patella Pb.

Indexed as

DNA MethylationEpigenesis, GeneticGene-Environment InteractionMaternal ExposureModels, Genetic11-beta-Hydroxysteroid Dehydrogenase Type 2AdultFemaleHumansInfant, NewbornInsulin-Like Growth Factor IILead PoisoningLong Interspersed Nucleotide ElementsMalePregnancyPrenatal Exposure Delayed Effects11-beta-Hydroxysteroid Dehydrogenase Type 2HSD11B2 protein, humanIGF2 protein, humanInsulin-Like Growth Factor IIANOVA, analysis of varianceDMR, differentially methylated regionDNA methylationELEMENT, early life exposures in Mexico to environmental toxicantsenvironmental exposureGEE, generalized estimating equationGLM, general linear modelH19, H19, imprinted maternally expressed transcript (non-protein coding)HSD11B2, hydroxysteroid (11-β) dehydrogenase 2IGF2, insulin-like growth factor 2K-XRF, K X-ray fluorescenceleadLINE-1, long interspersed element-1OLS, ordinary linear regressionPb, leadPCR, polymerase chain reactionpyrosequencingquality controlstatistical methods

Identifiers

PMID25580720
PMCPMC4622744
OpenAlexW2089939809

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.