Evidence map›Paper›PMID 36457128›Full record

ArticleClinical epigenetics2022

Incorporation of DNA methylation quantitative trait loci (mQTLs) in epigenome-wide association analysis: application to birthweight effects in neonatal whole blood.

Shaobo Li, Nicholas Mancuso, Catherine Metayer, Xiaomei Ma, Adam J de Smith, Joseph L Wiemels

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Clinical epigenetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed
0.8field-weighted citation impact, top 30% 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

7 citing papers in PubMed, 8 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. The Influence of DNA Repair Genes and Prenatal Tobacco Exposure on Risk of Childhood Acute Lymphoblastic Leukemia: A Gene-Environment Interaction Study.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2025
    Article
  6. Gene-Environment Analyses Reveal Novel Genetic Candidates with Prenatal Tobacco Exposure in Relation to Risk for Childhood Acute Lymphoblastic Leukemia.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2023
    Article
  7. 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

6 authors at 3 institutions in 1 country.

Shaobo LiDepartment of Population and Public Health Sciences, Center for Genetic Epidemiology, University of Southern California, USC Health Sciences Campus, 1520 San Pablo St., Los Angeles, CA, USA.
Nicholas MancusoDepartment of Population and Public Health Sciences, Center for Genetic Epidemiology, University of Southern California, USC Health Sciences Campus, 1520 San Pablo St., Los Angeles, CA, USA.
Catherine MetayerSchool of Public Health, University of California Berkeley, Berkeley, CA, USA.
Xiaomei MaDepartment of Chronic Disease Epidemiology, Yale School of Public Health, Yale University, New Haven, CT, USA.
Adam J de SmithDepartment of Population and Public Health Sciences, Center for Genetic Epidemiology, University of Southern California, USC Health Sciences Campus, 1520 San Pablo St., Los Angeles, CA, USA.
Joseph L WiemelsDepartment of Population and Public Health Sciences, Center for Genetic Epidemiology, University of Southern California, USC Health Sciences Campus, 1520 San Pablo St., Los Angeles, CA, USA. wiemels@usc.edu.
University of Southern California · USUniversity of California, Berkeley · USYale University · US

Funding

Environmental and Molecular Epidemiology of Childhood LeukemiaR01ES009137 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI METAYER, CATHERINE · 1999 to 2013
$21.1M
Genome-Wide Association Study of Childhood Leukemia by Hispanic StatusR01CA155461 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI MA, XIAOMEI, WIEMELS, JOSEPH LEO · 2011 to 2014
$4.1M
Project 3: Prenatal Exposure, DNA Methylation & Childhood LeukemiaP01ES018172 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI METAYER, CATHERINE · 2009 to 2013
$3.7M
Impact of low IL-10 levels at birth and leukemia riskR01CA185058 · NCI · UNIVERSITY OF CALIFORNIA, SAN FRANCISCO · PI KOGAN, SCOTT C., WIEMELS, JOSEPH LEO · 2014 to 2018
$3.1M
Perinatal immune development and risk of childhood acute lymphoblastic leukemiaR01CA175737 · NCI · UNIVERSITY OF SOUTHERN CALIFORNIA · PI MA, XIAOMEI, WIEMELS, JOSEPH LEO · 2014 to 2018
$3.0M
NCI NIH HHS R01 CA155461NCI NIH HHS R01 CA175737NCI NIH HHS R01 CA185058NIEHS NIH HHS P01 ES018172NIEHS NIH HHS R01 ES009137
6 · The paper itself

Abstract

backgroundEpigenome-wide association studies (EWAS) have helped to define the associations between DNA methylation and many clinicopathologic and developmental traits. Since DNA methylation is affected by genetic variation at certain loci, EWAS associations may be potentially influenced by genetic effects. However, a formal assessment of the value of incorporating genetic variation in EWAS evaluations is lacking especially for multiethnic populations.

methodsUsing single nucleotide polymorphism (SNP) from Illumina Omni Express or Affymetrix PMDA arrays and DNA methylation data from the Illumina 450 K or EPIC array from 1638 newborns of diverse genetic ancestries, we generated DNA methylation quantitative trait loci (mQTL) databases for both array types. We then investigated associations between neonatal DNA methylation and birthweight (incorporating gestational age) using EWAS modeling, and reported how EWAS results were influenced by controlling for mQTLs.

resultsFor CpGs on the 450 K array, an average of 15.4% CpGs were assigned as mQTLs, while on the EPIC array, 23.0% CpGs were matched to mQTLs (adjusted P value < 0.05). The CpGs associated with SNPs were enriched in the CpG island shore regions. Correcting for mQTLs in the EWAS model for birthweight helped to increase significance levels for top hits. For CpGs overlapping genes associated with birthweight-related pathways (nutrition metabolism, biosynthesis, for example), accounting for mQTLs changed their regression coefficients more dramatically (> 20%) than for other random CpGs.

conclusionDNA methylation levels at circa 20% CpGs in the genome were affected by common SNP genotypes. EWAS model fit significantly improved when taking these genetic effects into consideration. Genetic effects were stronger on CpGs overlapping genetic elements associated with control of gene expression.

Indexed as

EpigenomeQuantitative Trait LociBirth WeightCpG IslandsDNA MethylationHumansInfant, NewbornBirthweightDNA methylationDNA methylation quantitative trait loci (mQTL)Epigenome-wide association analysis (EWAS)

Identifiers

PMID36457128
PMCPMC9714153
OpenAlexW4310522730

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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.