Evidence map›Paper›PMID 32817202›Full record

ArticleNeurology(R) neuroimmunology & neuroinflammation2020

Phenome-wide examination of comorbidity burden and multiple sclerosis disease severity.

Tingting Zhang, Matthew Goodman, Feng Zhu, Brian Healy, Robert Carruthers, Tanuja Chitnis, Howard Weiner, Tianxi Cai, Philip De Jager, Helen Tremlett and 1 more

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

Article in Neurology(R) neuroimmunology & neuroinflammation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed, 1 pooled it
2.6field-weighted citation impact, top 9% 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

14 citing papers in PubMed, 1 synthesis or guideline pooled it, 25 citations in OpenAlex.

  1. Rituximab for people with multiple sclerosis.The Cochrane database of systematic reviews · 2025
    Pooled it
  2. Article
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  4. Assessment of the Multiple Sclerosis Severity Score and the Age-Related Multiple Sclerosis Severity Score as health indicators in a population-based cohort.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2025
    Article
  5. Clustering Sequence Data with Mixture Markov Chains with Covariates Using Multiple Simplex Constrained Optimization Routine (MSiCOR).Journal of computational and graphical statistics : a joint publication of American Statistical Association, Institute of Mathematical Statistics, Interface Foundation of North America · 2024
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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

11 authors at 1 institution in 2 countries.

Tingting ZhangFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Matthew GoodmanFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Feng ZhuFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Brian HealyFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Robert CarruthersFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Tanuja ChitnisFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Howard WeinerFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Tianxi CaiFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Philip De JagerFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Helen TremlettFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA.
Zongqi XiaFrom the Department of Health Services (T.Z.), Policy and Practice, Brown University, Providence, RI; Department of Biostatistics (M.G., T. Cai), Harvard T. H. Chan School of Public Health, Boston, MA; Department of Medicine (Neurology) (F.Z., R.C., H.T.), and the Djavad Mowafaghian Centre for Brain Health, University of British Columbia, Vancouver, Canada; Department of Neurology (B.H., T. Chitnis, H.W., P.D.J., Z.X.), Brigham and Women's Hospital, Boston, MA; Department of Neurology (P.D.J.), Columbia University, New York, NY; and Department of Neurology (Z.X.), University of Pittsburgh, PA. zxia1@pitt.edu.ORCID 0000-0003-1500-2589
Brigham and Women's Hospital · US

Funding

Leveraging electronic health records to optimize treatment selection and response in multiple sclerosisR01NS098023 · NINDS · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · PI Zongqi Xia · 2016 to 2026
$4.6M
CIHRNINDS NIH HHS R01 NS098023
6 · The paper itself

Abstract

objectiveWe assessed the comorbidity burden associated with multiple sclerosis (MS) severity by performing a phenome-wide association study (PheWAS).

methodsWe conducted a PheWAS in 2 independent cohorts: a discovery (Boston, United States; 1993-2014) and extension cohort (British Columbia, Canada; 1991-2008). We included adults with MS, ≥1 Expanded Disability Status Scale (EDSS) score, and ≥1

resultsThe discovery and extension cohorts included 3,439 and 4,876 participants, respectively. After Bonferroni correction and covariate adjustments, a higher MSSS was associated with 37 coexisting conditions in the discovery cohort. Subsequently, 16 conditions, including genitourinary, infectious, metabolic, epilepsy, and movement disorders, met the reporting criteria, reaching the Bonferroni threshold of significance with the same direction of effect in the discovery and extension cohort. Notably, benign neoplasm of the skin was inversely associated with the MSSS.

conclusionThe phenome-wide approach enabled a systematic interrogation of the comorbidity burden and highlighted clinically relevant medical conditions associated with MS severity (beyond MS-specific consequences) and defines a roadmap for comprehensive investigation of comorbidities in chronic neurologic diseases. Further prospective investigation of the bidirectional relationship between disability and comorbidities could inform the individualized patient management.

Indexed as

ComorbidityGenetic Association StudiesPhenotypeAdultBostonBritish ColumbiaCohort StudiesFemaleGenome-Wide Association StudyHumansMaleMiddle AgedMultiple SclerosisSeverity of Illness IndexYoung Adult

Identifiers

PMID32817202
PMCPMC7673286
OpenAlexW3079330638

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-ND
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 OpenQuestion graph.