Evidence map›Paper›PMID 23244307›Full record

ArticleEpigenomics2012

MBD-seq as a cost-effective approach for methylome-wide association studies: demonstration in 1500 case--control samples.

Karolina A Aberg, Joseph L McClay, Srilaxmi Nerella, Lin Y Xie, Shaunna L Clark, Alexandra D Hudson, Jozsef Bukszár, Daniel Adkins, Swedish Schizophrenia Consortium, Christina M Hultman and 3 more

Abstract read
In one paragraph

Article in Epigenomics, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
50citing papers in PubMed, 2 pooled it
–field-weighted citation impact
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

50 citing papers in PubMed, 2 syntheses or guidelines pooled it.

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  18. Epigenetic Aging in Major Depressive Disorder.The American journal of psychiatry · 2018
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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

13 authors.

Karolina A AbergCenter for Biomarker Research & Personalized Medicine, School of Pharmacy, Virginia Commonwealth University, Richmond, VA 23298, USA.
Joseph L McClay
Srilaxmi Nerella
Lin Y Xie
Shaunna L Clark
Alexandra D Hudson
Jozsef Bukszár
Daniel Adkins
Swedish Schizophrenia Consortium
Christina M Hultman
Patrick F Sullivan
Patrik K E Magnusson
Edwin J C G van den Oord

Funding

A Large-Scale Schizophrenia Association Study in SwedenR01MH077139 · NIMH · UNIV OF NORTH CAROLINA CHAPEL HILL · PI SULLIVAN, PATRICK F · 2007 to 2018
$9.9M
Whole genome profiling to detect schizophrenia methylation markersRC2MH089996 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI VAN DEN OORD, EDWIN · 2009 to 2010
$4.5M
Integrating Genomic and Environmental Perspectives on Internalizing DisordersK01MH093731 · NIMH · VIRGINIA COMMONWEALTH UNIVERSITY · PI ADKINS, DANIEL E · 2011 to 2015
$649k
Investigating Methylation Patterns Associated with Alcohol Use and AddictionK01AA021266 · NIAAA · VIRGINIA COMMONWEALTH UNIVERSITY · PI CLARK, SHAUNNA L · 2012 to 2016
$580k
NIAAA NIH HHS K01 AA021266NIMH NIH HHS K01 MH093731NIMH NIH HHS MH077139NIMH NIH HHS R01 MH077139NIMH NIH HHS RC2 MH089996NIMH NIH HHS RC2MH089996
6 · The paper itself

Abstract

aimWe studied the use of methyl-CpG binding domain (MBD) protein-enriched genome sequencing (MBD-seq) as a cost-effective screening tool for methylome-wide association studies (MWAS). MATERIALS &

methodsBecause MBD-seq has not yet been applied on a large scale, we first developed and tested a pipeline for data processing using 1500 schizophrenia cases and controls plus 75 technical replicates with an average of 68 million reads per sample. This involved the use of technical replicates to optimize quality control for multi- and duplicate-reads, an in silico experiment to identify CpGs in loci with alignment problems, CpG coverage calculations based on multiparametric estimates of the fragment size distribution, a two-stage adaptive algorithm to combine data from correlated adjacent CpG sites, principal component analyses to control for confounders and new software tailored to handle the large data set.

resultsWe replicated MWAS findings in independent samples using a different technology that provided single base resolution. In an MWAS of age-related methylation changes, one of our top findings was a previously reported robust association involving GRIA2. Our results also suggested that owing to the many confounding effects, a considerable challenge in MWAS is to identify those effects that are informative about disease processes.

conclusionThis study showed the potential of MBD-seq as a cost-effective tool in large-scale disease studies.

Indexed as

DNA MethylationGenetic Association StudiesGenome, HumanCase-Control StudiesCpG IslandsDNA-Binding ProteinsHigh-Throughput Nucleotide SequencingHumansReceptors, AMPASchizophreniaSequence Analysis, DNADNA-Binding Proteinsglutamate receptor ionotropic, AMPA 2Receptors, AMPA

Identifiers

PMID23244307
PMCPMC3923085

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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.