CoChat
Sign Up
Cited by 114Genetic Associations and EpidemiologyGenetic Mapping and Diversity in Plants and AnimalsDiabetes and associated disorders

The DOI matches its Crossref record; 14 of the 14 references it cites were found in a registry or an index.

Statistical independence of the colocalized association signals for type 1 diabetes and RPS26 gene expression on chromosome 12q13

Open access
Plagnol, Vincent, Smyth, Deborah J., Todd, John A., Clayton, David G.·2009·Biostatistics
DOI 10.1093/biostatistics/kxn039PMC PMC2648905
Open this paper in CoChat — free accountOpen PDF

Abstract

Following the recent success of genome-wide association studies in uncovering disease-associated genetic variants, the next challenge is to understand how these variants affect downstream pathways. The most proximal trait to a disease-associated variant, most commonly a single nucleotide polymorphism (SNP), is differential gene expression due to the cis effect of SNP alleles on transcription, translation, and/or splicing gene expression quantitative trait loci (eQTL). Several genome-wide SNP-gene expression association studies have already provided convincing evidence of widespread association of eQTLs. As a consequence, some eQTL associations are found in the same genomic region as a disease variant, either as a coincidence or a causal relationship. Cis-regulation of RPS26 gene expression and a type 1 diabetes (T1D) susceptibility locus have been colocalized to the 12q13 genomic region. A recent study has also suggested RPS26 as the most likely susceptibility gene for T1D in this genomic region. However, it is still not clear whether this colocalization is the result of chance alone or if RPS26 expression is directly correlated with T1D susceptibility, and therefore, potentially causal. Here, we derive and apply a statistical test of this hypothesis. We conclude that RPS26 expression is unlikely to be the molecular trait responsible for T1D susceptibility at this locus, at least not in a direct, linear connection.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1093/biostatistics/kxn039

Cites

14 of 14 references verified0 citation errors · 0 not checkable

Statistics

Figures

Fig. 1. Correlation between RPS26 expression and rs1131017 genotypes. RPS26 expression was measured using the Affymetrix HG-U133 Plus 2.0 gene expression chip.
Fig. 1. Correlation between RPS26 expression and rs1131017 genotypes. RPS26 expression was measured using the Affymetrix HG-U133 Plus 2.0 gene expression chip.CC BY-NC · PubMed Central
Fig. 2. Comparison of estimated regression coefficients in the T1D case–control and the eQTL RPS26 expression studies, analyzing 1 SNP at a time. Assuming a sole causal variant for both traits, the estimated regression coefficients should be proportional between both studies.
Fig. 2. Comparison of estimated regression coefficients in the T1D case–control and the eQTL RPS26 expression studies, analyzing 1 SNP at a time. Assuming a sole causal variant for both traits, the estimated regression coefficients should be proportional between both studies.CC BY-NC · PubMed Central
Fig. 3. (A) Jointly estimated regression coefficients and confidence intervals for rs1131017 and rs705704 under the null hypothesis 0 of a sole common variant and under the alternative 1. Under the null hypothesis 0, estimated regression coefficients have to be located on a line passing through the origin. (B) Rescaled version of (A) highlighting the fact that when compared on the same unit scale (i.e. regression estimates located on the unit circle), the variance of the estimated coefficients is higher for the T1D study. Therefore, regression estimates under the null are driven by the RPS26 expression data.
Fig. 3. (A) Jointly estimated regression coefficients and confidence intervals for rs1131017 and rs705704 under the null hypothesis 0 of a sole common variant and under the alternative 1. Under the null hypothesis 0, estimated regression coefficients have to be located on a line passing through the origin. (B) Rescaled version of (A) highlighting the fact that when compared on the same unit scale (i.e. regression estimates located on the unit circle), the variance of the estimated coefficients is higher for the T1D study. Therefore, regression estimates under the null are driven by the RPS26 expression data.CC BY-NC · PubMed Central

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 14 references

Cited by

Sorted by citations

Related

See all

Metadata

Authors
Plagnol, V., Smyth, D. J., Todd, J. A., & Clayton, D. G.
Affiliations
University of Cambridge (GB)
Corresponding author
Plagnol, Vincent
ORCID
Venue
Biostatistics
Publisher
Oxford University Press (OUP)
Published
2008-11-27
Volume
10
Issue
2
Pages
327-334
ISSN
  • 1465-4644 (ISSN-L)
  • 1468-4357
DOI
10.1093/biostatistics/kxn039
PMC
PMC2648905
OpenAlex
W2160717726
Cited by
113
References
14
Citations by year
2026: 6 · 2025: 10 · 2024: 9 · 2023: 8 · 2022: 10 · 2021: 19 · 2020: 8 · 2019: 5 · 2018: 3 · 2016: 1 · 2015: 5 · 2014: 4 · 2013: 6 · 2012: 5
FWCI
2.66
Type
journal article
Language
en
Open access
Licence
cc-by-nc
Locations
  • Biostatistics (publishedVersion, cc-by-nc)
  • PubMed Central (publishedVersion, cc-by-nc)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
  • Wellcome Trust (061858, 079895)
  • National Institute for Health and Care Research (NF-SI-0508-10275)
  • Cambridge Institute for Medical Research, University of Cambridge (079895)
  • NIHR Cambridge Biomedical Research Centre
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Mapping and Diversity in Plants and Animals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Diabetes and associated disorders
Keywords
type 1 diabetes, RPS26, expression quantitative trait loci, colocalization, cis-regulation, chromosome 12q13, single nucleotide polymorphisms, causal inference
MeSH terms
Chromosome Mapping, Chromosomes, Human, Pair 12, Diabetes Mellitus, Type 1, Humans, Models, Genetic, Ribosomal Proteins, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Genome-Wide Association Study

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review