Evidence map›Paper›PMID 25884492›Full record

ArticleBMC genomics2015

MicroRNAs enrichment in GWAS of complex human phenotypes.

Luiz F Goulart, Francesco Bettella, Ida E Sønderby, Andrew J Schork, Wesley K Thompson, Morten Mattingsdal, Vidar M Steen, Verena Zuber, Yunpeng Wang, Anders M Dale and 3 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in BMC genomics, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed, 1 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

10 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. MicroRNA Milk Exosomes: From Cellular Regulator to Genomic Marker.Animals : an open access journal from MDPI · 2020
    Review
  4. The developmental-genetics of canalization.Seminars in cell & developmental biology · 2019
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Review
  10. Review
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.

Luiz F GoulartNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. luiz.goulart@medisin.uio.no.
Francesco BettellaNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. checco74@gmail.com.
Ida E SønderbyNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. i.e.sonderby@medisin.uio.no.
Andrew J SchorkMultimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, 92037, USA. ajschork@cogsci.ucsd.edu.
Wesley K ThompsonDepartment of Psychiatry, University of California at San Diego, La Jolla, CA, 92037, USA. wes.stat@gmail.com.
Morten MattingsdalNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. morten.mattingsdal@gmail.com.
Vidar M SteenNORMENT, KG Jebsen Centre for Psychosis Research, Department of Clinical Science, University of Bergen, Bergen, Norway. vidar.martin.steen@helse-bergen.no.
Verena ZuberNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. verena.zuber@ncmm.uio.no.
Yunpeng WangNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. yunpeng.wng@gmail.com.
Anders M DaleMultimodal Imaging Laboratory, University of California at San Diego, La Jolla, CA, 92037, USA. amdale@ucsd.edu.
PRACTICAL/ELLIPSE consortium
Ole A AndreassenNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. o.a.andreassen@medisin.uio.no.
Srdjan DjurovicNORMENT, KG Jebsen Centre for Psychosis Research, Institute of Clinical Medicine, University of Oslo, Oslo, Norway. srdjan.djurovic@medisin.uio.no.

Funding

Polygenicity, Pleiotrophy and Power: Novel Statistical Methods for Gene DiscoveryR01GM104400 · NIGMS · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI THOMPSON, WESLEY KURT · 2014 to 2017
$1.6M
Cancer Research UK 15007Cancer Research UK 17528NIGMS NIH HHS R01 GM104400
6 · The paper itself

Abstract

backgroundThe genotype information carried by Genome-wide association studies (GWAS) seems to have the potential to explain more of the 'missing heritability' of complex human phenotypes, given improved statistical approaches. Several lines of evidence support the involvement of microRNA (miRNA) and other non-coding RNA in complex human traits and diseases. We employed a novel, genetic annotation-informed enrichment method for GWAS that captures more polygenic effects than standard GWAS analysis, to investigate if miRNA-tagging Single Nucleotide Polymorphisms (SNPs) are enriched of associations with 15 complex human phenotypes. We then leveraged the enrichment using a conditional False Discovery Rate (condFDR) approach to assess any improvement in the detection of individual miRNA SNPs associated with the disorders.

resultsWe found SNPs tagging miRNA transcription regions to be significantly enriched of associations with 10 of 15 phenotypes. The enrichment remained significant after controlling for affiliation to other genomic categories, and was confirmed by replication. Albeit only nominally significant, enrichment was found also in miRNA binding sites for 10 phenotypes out of 15. Leveraging the enrichment in the condFDR framework, we observed a 2-4-fold increase in discovery of SNPs tagging miRNA regions.

conclusionsOur results suggest that miRNAs play an important role in the polygenic architecture of complex human disorders and traits, and therefore that miRNAs are a genomic category that can and should be used to improve gene discovery.

Indexed as

Genome, HumanGenome-Wide Association StudyBinding SitesCrohn DiseaseDatabases, GeneticGenotypeHumansLinkage DisequilibriumLipoproteins, LDLMicroRNAsPhenotypePolymorphism, Single NucleotideSchizophreniaLipoproteins, LDLMicroRNAs

Identifiers

PMID25884492
PMCPMC4437677

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.