Evidence map›Paper›PMID 20043853›Full record

ArticleBMC medical genomics2009

Prioritizing genes for follow-up from genome wide association studies using information on gene expression in tissues relevant for type 2 diabetes mellitus.

Hemang Parikh, Valeriya Lyssenko, Leif C Groop

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

Article in BMC medical genomics, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.3field-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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 46 citations in OpenAlex.

  1. Pooled it
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  13. The genetics of familial combined hyperlipidaemia.Nature reviews. Endocrinology · 2012
    Review
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  16. A draft sequence of the Neandertal genome.Science (New York, N.Y.) · 2010
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  19. The relationship between case-control differential gene expression from brain tissue and genetic associations in schizophrenia.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
    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

3 authors at 2 institutions in 3 countries.

Hemang ParikhDepartment of Clinical Sciences, Diabetes and Endocrinology, Lund University, University Hospital Malmö, Malmö, Sweden. parikhhm@mail.nih.gov
Valeriya Lyssenko
Leif C Groop
Lund University · SEUniversity of Helsinki · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundGenome-wide association studies (GWAS) have emerged as a powerful approach for identifying susceptibility loci associated with polygenetic diseases such as type 2 diabetes mellitus (T2DM). However, it is still a daunting task to prioritize single nucleotide polymorphisms (SNPs) from GWAS for further replication in different population. Several recent studies have shown that genetic variation often affects gene-expression at proximal (cis) as well as distal (trans) genomic locations by different mechanisms such as altering rate of transcription or splicing or transcript stability.

methodsTo prioritize SNPs from GWAS, we combined results from two GWAS related to T2DM, the Diabetes Genetics Initiative (DGI) and the Wellcome Trust Case Control Consortium (WTCCC), with genome-wide expression data from pancreas, adipose tissue, liver and skeletal muscle of individuals with or without T2DM or animal models thereof to identify T2DM susceptibility loci.

resultsWe identified 1,170 SNPs associated with T2DM with P < 0.05 in both GWAS and 243 genes that were located in the vicinity of these SNPs. Out of these 243 genes, we identified 115 differentially expressed in publicly available gene expression profiling data. Notably five of them, IGF2BP2, KCNJ11, NOTCH2, TCF7L2 and TSPAN8, have subsequently been shown to be associated with T2DM in different populations. To provide further validation of our approach, we reversed the approach and started with 26 known SNPs associated with T2DM and related traits. We could show that 12 (57%) (HHEX, HNF1B, IGF2BP2, IRS1, KCNJ11, KCNQ1, NOTCH2, PPARG, TCF7L2, THADA, TSPAN8 and WFS1) out of 21 genes located in vicinity of these SNPs were showing aberrant expression in T2DM from the gene expression profiling studies.

conclusionsUtilizing of gene expression profiling data from different tissues of individuals with or without T2DM or animal models thereof is a powerful tool for prioritizing SNPs from WGAS for further replication studies.

Indexed as

Gene Expression ProfilingGenome-Wide Association StudyAnimalsDiabetes Mellitus, Type 2Follow-Up StudiesHumansMiceOligonucleotide Array Sequence AnalysisOrgan SpecificityPolymorphism, Single NucleotideRatsReproducibility of Results

Identifiers

PMID20043853
PMCPMC2815699
OpenAlexW1976588209

What OpenQuestion holds

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LicenceCC BY
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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.