Evidence map›Paper›PMID 35717575›Full record

ArticleHuman molecular genetics2022

Investigating DNA methylation as a mediator of genetic risk in childhood acute lymphoblastic leukemia.

Keren Xu, Shaobo Li, Priyatama Pandey, Alice Y Kang, Libby M Morimoto, Nicholas Mancuso, Xiaomei Ma, Catherine Metayer, Joseph L Wiemels, Adam J de Smith

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

Article in Human molecular genetics, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed
0.3field-weighted citation impact, top 45% 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

4 citing papers in PubMed, 4 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. 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

10 authors at 3 institutions in 1 country.

Keren XuCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90033, USA.ORCID 0000-0003-4615-2459
Shaobo LiCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Priyatama PandeyCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Alice Y KangSchool of Public Health, University of California, Berkeley, Berkeley, CA 94704, USA.
Libby M MorimotoSchool of Public Health, University of California, Berkeley, Berkeley, CA 94704, USA.
Nicholas MancusoCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Xiaomei MaDepartment of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT 06510, USA.
Catherine MetayerSchool of Public Health, University of California, Berkeley, Berkeley, CA 94704, USA.
Joseph L WiemelsCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90033, USA.
Adam J de SmithCenter for Genetic Epidemiology, Department of Population and Public Health Sciences, University of Southern California, Los Angeles, CA 90033, USA.
University of Southern California · USUniversity of California, Berkeley · USYale University · US

Funding

Training CoreP42ES004705 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI SMITH, MARTYN T · 1987 to 2025
$74.6M
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 Exposures, Constitutive Genetics, DNA Methylation & Childhood LeukemiaP50ES018172 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI METAYER, CATHERINE · 2015 to 2019
$3.8M
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
Support For Infrastructure of Childhood Leukemia Environmental ResearchR24ES028524 · NIEHS · UNIVERSITY OF CALIFORNIA BERKELEY · PI Catherine Metayer · 2017 to 2026
$2.3M
NCCDPHP CDC HHS U58 DP003862NCI NIH HHS HHSN261201000034CNCI NIH HHS HHSN261201000035CNCI NIH HHS HHSN261201000035INCI NIH HHS HHSN261201000140CNCI NIH HHS R01 CA155461NCI NIH HHS R01 CA175737NCI NIH HHS R01CA175737NIEHS NIH HHS P42 ES004705NIEHS NIH HHS P50 ES018172NIEHS NIH HHS R01 ES009137NIEHS NIH HHS R24 ES028524NIH HHS R01CA155461
6 · The paper itself

Abstract

Genome-wide association studies have identified a growing number of single nucleotide polymorphisms (SNPs) associated with childhood acute lymphoblastic leukemia (ALL), yet the functional roles of most SNPs are unclear. Multiple lines of evidence suggest that epigenetic mechanisms may mediate the impact of heritable genetic variation on phenotypes. Here, we investigated whether DNA methylation mediates the effect of genetic risk loci for childhood ALL. We performed an epigenome-wide association study (EWAS) including 808 childhood ALL cases and 919 controls from California-based studies using neonatal blood DNA. For differentially methylated CpG positions (DMPs), we next conducted association analysis with 23 known ALL risk SNPs followed by causal mediation analyses addressing the significant SNP-DMP pairs. DNA methylation at CpG cg01139861, in the promoter region of IKZF1, mediated the effects of the intronic IKZF1 risk SNP rs78396808, with the average causal mediation effect (ACME) explaining ~30% of the total effect (ACME P = 0.0031). In analyses stratified by self-reported race/ethnicity, the mediation effect was only significant in Latinos, explaining ~41% of the total effect of rs78396808 on ALL risk (ACME P = 0.0037). Conditional analyses confirmed the presence of at least three independent genetic risk loci for childhood ALL at IKZF1, with rs78396808 unique to non-European populations. We also demonstrated that the most significant DMP in the EWAS, CpG cg13344587 at gene ARID5B (P = 8.61 × 10-10), was entirely confounded by the ARID5B ALL risk SNP rs7090445. Our findings provide new insights into the functional pathways of ALL risk SNPs and the DNA methylation differences associated with risk of childhood ALL.

Indexed as

DNA MethylationPrecursor Cell Lymphoblastic Leukemia-LymphomaGenome-Wide Association StudyHumansPolymorphism, Single NucleotideTranscription FactorsTranscription Factors

Identifiers

PMID35717575
PMCPMC9616572
OpenAlexW4283123568

What OpenQuestion holds

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Registered trials

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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.