Evidence map›Paper›PMID 39241920›Full record

SynthesisClinical immunology (Orlando, Fla.)2024

Leveraging pleiotropy identifies common-variant associations with selective IgA deficiency.

Thomas W Willis, Effrossyni Gkrania-Klotsas, Nicholas J Wareham, Eoin F McKinney, Paul A Lyons, Kenneth G C Smith, Chris Wallace

Abstract readMeta-Analysis
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Clinical immunology (Orlando, Fla.), 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

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

1 citing paper in PubMed.

  1. 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

7 authors.

Thomas W WillisMedical Research Council Biostatistics Unit, University of Cambridge, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK. Electronic address: thomas.willis@mrc-bsu.cam.ac.uk.
Effrossyni Gkrania-KlotsasMedical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK; Department of Infectious Diseases, Cambridge University Hospital NHS Foundation Trust, Cambridge, UK.
Nicholas J WarehamMedical Research Council Epidemiology Unit, University of Cambridge, Cambridge, UK.
Eoin F McKinneyCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
Paul A LyonsCambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.
Kenneth G C SmithWalter and Eliza Hall Institute of Medical Research, Melbourne, Australia; Department of Medical Biology, University of Melbourne, Melbourne, Australia.
Chris WallaceMedical Research Council Biostatistics Unit, University of Cambridge, Cambridge, UK; Cambridge Institute of Therapeutic Immunology and Infectious Disease, University of Cambridge, Cambridge, UK; Department of Medicine, University of Cambridge, Cambridge, UK.

Funding

Medical Research Council MC_UU_00002/4Medical Research Council MC_UU_00006/1Medical Research Council MC_UU_12015/1Medical Research Council MR/N003284/1Wellcome Trust 107881Wellcome Trust 219506Wellcome Trust 220788
6 · The paper itself

Abstract

Selective IgA deficiency (SIgAD) is the most common inborn error of immunity (IEI). Unlike many IEIs, evidence of a role for highly penetrant rare variants in SIgAD is lacking. Previous SIgAD studies have had limited power to identify common variants due to their small sample size. We overcame this problem first through meta-analysis of two existing GWAS. This identified four novel common-variant associations and enrichment of SIgAD-associated variants in genes linked to Mendelian IEIs. SIgAD showed evidence of shared genetic architecture with serum IgA and a number of immune-mediated diseases. We leveraged this pleiotropy through the conditional false discovery rate procedure, conditioning our SIgAD meta-analysis on large GWAS of asthma and rheumatoid arthritis, and our own meta-analysis of serum IgA. This identified an additional 18 variants, increasing the number of known SIgAD-associated variants to 27 and strengthening the evidence for a polygenic, common-variant aetiology for SIgAD.

Indexed as

Genetic PleiotropyIgA DeficiencyImmunoglobulin AAsthmaGenetic Predisposition to DiseaseGenome-Wide Association StudyHumansPolymorphism, Single NucleotideImmunoglobulin AGWASimmunodeficiencyimmunoglobulin Apleiotropy

Identifiers

PMID39241920
PMCPMC7618579

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

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 Socratic graph.