Evidence map›Paper›PMID 26007630›Full record

SynthesisNature communications2015

Variants in ELL2 influencing immunoglobulin levels associate with multiple myeloma.

Bhairavi Swaminathan, Guðmar Thorleifsson, Magnus Jöud, Mina Ali, Ellinor Johnsson, Ram Ajore, Patrick Sulem, Britt-Marie Halvarsson, Guðmundur Eyjolfsson, Vilhelmina Haraldsdottir and 24 more

Open access · goldAbstract readMeta-AnalysisMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Synthesis in Nature communications, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 6 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
59citing papers in PubMed, 6 pooled it
45.2field-weighted citation impact, top 1% 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

59 citing papers in PubMed, 6 syntheses or guidelines pooled it, 1,208 citations in OpenAlex.

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  20. The Norwegian childhood cancer biobank.Cancer reports (Hoboken, N.J.) · 2022
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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

34 authors at 14 institutions in 5 countries.

Bhairavi SwaminathanHematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden.
Guðmar ThorleifssondeCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Magnus Jöud1] Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden [2] Clinical Immunology and Transfusion Medicine, Laboratory Medicine, Office of Medical Services, Akutgatan 8, SE-221 85 Lund, Sweden.
Mina AliHematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden.
Ellinor JohnssonHematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden.
Ram AjoreHematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden.
Patrick SulemdeCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.ORCID 0000000171236123
Britt-Marie HalvarssonHematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden.
Guðmundur EyjolfssonThe Laboratory in Mjodd, IS-109 Reykjavik, Iceland.
Vilhelmina HaraldsdottirDepartment of Hematology, Landspitali, The National University Hospital of Iceland, IS-101 Reykjavik, Iceland.
Christina HultmanDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Erik IngelssonDepartment of Medical Sciences, Molecular Epidemiology and Science for Life Laboratory, Uppsala University, SE-751 85 Uppsala, Sweden.
Sigurður Y KristinssonFaculty of Medicine, University of Iceland, IS-101 Reykjavik, Iceland.
Anna K KählerDepartment of Medical Epidemiology and Biostatistics, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Stig LenhoffHematology Clinic, Skåne University Hospital, SE-221 85 Lund, Sweden.
Gisli MassondeCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Ulf-Henrik MellqvistSection of Hematology, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden.
Robert MånssonCenter for Hematology and Regenerative Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Sven NelanderDepartment of Immunology, Pathology and Genetics, Uppsala University, Rudbeck Laboratory, SE-751 05 Uppsala, Sweden.
Isleifur OlafssonDepartment of Clinical Biochemistry, Landspitali, The National University Hospital of Iceland, IS-101 Reykjavik, Iceland.
Olof SigurðardottirDepartment of Clinical Biochemistry, Akureyri Hospital, IS-600 Akureyri, Iceland.
Hlif SteingrimsdóttirDepartment of Hematology, Landspitali, The National University Hospital of Iceland, IS-101 Reykjavik, Iceland.
Annette VangstedDepartment of Haematology, University Hospital of Copenhagen at Rigshospitalet, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Ulla VogelNational Research Centre for the Working Environment, Lersø Parkallé 105, DK-2100 Copenhagen, Denmark.
Anders WaageDepartment of Cancer Research and Molecular Medicine, Norwegian University of Science and Technology, Box 8905, N-7491 Trondheim, Norway.
Hareth NahiCenter for Hematology and Regenerative Medicine, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Daniel F GudbjartssondeCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Thorunn RafnardeCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Ingemar TuressonHematology Clinic, Skåne University Hospital, SE-221 85 Lund, Sweden.
Urban GullbergHematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden.
Kári StefánssondeCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Markus Hansson1] Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden [2] Hematology Clinic, Skåne University Hospital, SE-221 85 Lund, Sweden.ORCID 0000000277154548
Unnur ThorsteinsdóttirdeCODE genetics, Sturlugata 8, IS-101 Reykjavik, Iceland.
Björn Nilsson1] Hematology and Transfusion Medicine, Department of Laboratory Medicine, Lund University, BMC B13, SE-221 84 Lund, Sweden [2] Clinical Immunology and Transfusion Medicine, Laboratory Medicine, Office of Medical Services, Akutgatan 8, SE-221 85 Lund, Sweden [3] Broad Institute, 7 Cambridge Center, Cambridge, Massachusetts 02142, USA.
Lund University · SEdeCODE Genetics (Iceland) · ISKarolinska Institutet · SENational University Hospital of Iceland · ISSkåne University Hospital · SEUppsala University · SEAkureyri Hospital · ISBroad Institute · USCopenhagen University Hospital · DKInnovation Center Iceland · ISNational Research Centre for the Working Environment · DKNorwegian University of Science and Technology · NOSahlgrenska University Hospital · SEUniversity of Iceland · IS

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Multiple myeloma (MM) is characterized by an uninhibited, clonal growth of plasma cells. While first-degree relatives of patients with MM show an increased risk of MM, the genetic basis of inherited MM susceptibility is incompletely understood. Here we report a genome-wide association study in the Nordic region identifying a novel MM risk locus at ELL2 (rs56219066T; odds ratio (OR)=1.25; P=9.6 × 10(-10)). This gene encodes a stoichiometrically limiting component of the super-elongation complex that drives secretory-specific immunoglobulin mRNA production and transcriptional regulation in plasma cells. We find that the MM risk allele harbours a Thr298Ala missense variant in an ELL2 domain required for transcription elongation. Consistent with a hypomorphic effect, we find that the MM risk allele also associates with reduced levels of immunoglobulin A (IgA) and G (IgG) in healthy subjects (P=8.6 × 10(-9) and P=6.4 × 10(-3), respectively) and, potentially, with an increased risk of bacterial meningitis (OR=1.30; P=0.0024).

Indexed as

Genetic Predisposition to DiseaseGenome-Wide Association StudyHumansImmunoglobulin AImmunoglobulin GIntracellular Signaling Peptides and ProteinsMeningitis, BacterialMultiple MyelomaProteinsTranscriptional Elongation FactorsELL2 protein, humanImmunoglobulin AImmunoglobulin GIntracellular Signaling Peptides and ProteinsProteinsTOM1 protein, humanTranscriptional Elongation Factors

Identifiers

PMID26007630
PMCPMC4455110
OpenAlexW1818450144

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.