Evidence map›Paper›PMID 39677438›Full record

ArticlemedRxiv : the preprint server for health sciences2024

GWAS highlights the neuronal contribution to multiple sclerosis susceptibility.

Lu Zeng, Khan Atlas, Tsering Lama, International Multiple Sclerosis Genetics Consortium, Tanuja Chitnis, Howard Weiner, Gao Wang, Masashi Fujita, Frauke Zipp, Mariko Taga and 2 more

Abstract readPreprint
PubMed Full text at PMC Publisher
In one paragraph

Article in medRxiv : the preprint server for health sciences, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing 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

0 citing papers in PubMed.

No citing paper in PubMed yet.

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

12 authors.

Lu ZengCenter for Translational and Computational Neuroimmunology & Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Khan AtlasDivision of Nephrology, Dept of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
Tsering LamaCenter for Translational and Computational Neuroimmunology & Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
International Multiple Sclerosis Genetics Consortium
Tanuja ChitnisAnne Romney Center for Neurologic Diseases and Brigham Multiple Sclerosis Center, Department of Neurology, Brigham & Women's Hospital, Boston MA.
Howard WeinerAnne Romney Center for Neurologic Diseases and Brigham Multiple Sclerosis Center, Department of Neurology, Brigham & Women's Hospital, Boston MA.
Gao WangThe Gertrude H. Sergievsky Center and the Department of Neurology, Columbia University, New York, NY, USA.
Masashi FujitaCenter for Translational and Computational Neuroimmunology & Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Frauke ZippDepartment of Neurology and Focus Program Translational Neuroscience (FTN), Rhine Main Neuroscience Network (rmn2), University Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
Mariko TagaCenter for Translational and Computational Neuroimmunology & Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.
Krzysztof KirylukDivision of Nephrology, Dept of Medicine, Vagelos College of Physicians & Surgeons, Columbia University, New York, NY, USA.
Philip L De JagerCenter for Translational and Computational Neuroimmunology & Columbia Multiple Sclerosis Center, Department of Neurology, Columbia University Irving Medical Center, New York, NY, USA.ORCID 0000-0002-8057-2505

Funding

Multi-omic network-directed proteoform discovery, dissection and functional validation to prioritize novel AD therapeutic targetsU01AG061356 · NIA · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI BENNETT, DAVID ALAN, DE JAGER, PHILIP L · 2018 to 2022
$13.7M
Predictive utility of polygenic risk scores for chronic kidney disease.K25DK128563 · NIDDK · COLUMBIA UNIVERSITY HEALTH SCIENCES · PI KHAN, ATLAS · 2021 to 2025
$846k
NIA NIH HHS U01 AG061356NIDDK NIH HHS K25 DK128563
6 · The paper itself

Abstract

Multiple Sclerosis (MS) is a chronic inflammatory and neurodegenerative disease affecting the brain and spinal cord. Genetic studies have identified many risk loci, that were thought to primarily impact immune cells and microglia. Here, we performed a multi-ancestry genome-wide association study with 20,831 MS and 729,220 control participants, identifying 236 susceptibility variants outside the Major Histocompatibility Complex, including four novel loci. We derived a polygenic score for MS and, optimized for European ancestry, it is informative for African-American and Latino participants. Integrating single-cell data from blood and brain tissue, we identified 76 genes affected by MS risk variants. Notably, while T cells showed the strongest enrichment, inhibitory neurons emerged as a key cell type, highlighting the importance of neuronal and glial dysfunction in MS susceptibility.

Identifiers

PMID39677438
PMCPMC11643295

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.