Evidence map›Paper›PMID 39270152›Full record

ArticleNeurology2024

Association of Polygenic Risk Score With Lifetime Risk of Developing Multiple Sclerosis in a Population-Based Birth-Year Cohort.

Floor C Loonstra, Daniel Álvarez Sirvent, Niccoló Tesi, Henne Holstege, Eva M M Strijbis, Alex N Salazar, Marc Hulsman, Sven J Van Der Lee, Bernard Uitdehaag

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In one paragraph

Article in Neurology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Polygenic risk scores in neurological disorders: restless legs syndrome as a translational model.Medizinische Genetik : Mitteilungsblatt des Berufsverbandes Medizinische Genetik e.V · 2026
    Article
  2. Is there a link between multiple sclerosis and Alzheimer disease? A critical note.Journal of neural transmission (Vienna, Austria : 1996) · 2026
    Review
  3. Towards primary prevention of multiple sclerosis.Nature reviews. Neurology · 2026
    Review
  4. Article
  5. Review
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

9 authors.

Floor C LoonstraFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.ORCID 0000-0002-1644-4410
Daniel Álvarez SirventFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.
Niccoló TesiFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.
Henne HolstegeFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.ORCID 0000-0002-7688-3087
Eva M M StrijbisFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.ORCID 0000-0001-6705-5864
Alex N SalazarFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.
Marc HulsmanFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.
Sven J Van Der LeeFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.ORCID 0000-0003-1606-8643
Bernard UitdehaagFrom the MS Center Amsterdam (F.C.L., E.M.M.S., B.U.), Neurology, Amsterdam Neuroscience, Genomics of Neurodegenerative Diseases and Aging (D.Á.S., N.T., H.H., A.N.S., M.H., S.J.V.D.L.), Human Genetics, and Alzheimer Center Amsterdam (H.H., S.J.V.D.L.), Neurology, Vrije Universiteit Amsterdam, Amsterdam UMC location VUmc; Delft Bioinformatics Lab (N.T., H.H.), Delft University of Technology; and Amsterdam Neuroscience (H.H., S.J.V.D.L.), Neurodegeneration, the Netherlands.ORCID 0000-0002-9226-7364

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

BACKGROUND AND

objectivesMore than 200 genetic variants have been associated with multiple sclerosis (MS) susceptibility. However, it is unclear to what extent genetic factors influence lifetime risk of MS. Using a population-based birth-year cohort, we investigate the effect of genetics on lifetime risk of MS.

methodsIn the Project Y study, we tracked down almost all persons with MS (pwMS) from birth year 1966 in the Netherlands. As control participants, we included non-MS participants from the Project Y cohort (born 1965-1967 in the Netherlands) and non-MS participants from the Amsterdam Dementia Cohort born between 1963 and 1969. Genetic variants associated with MS were determined in pwMS and control participants using genotyping or imputation methods. Polygenic risk scores (PRSs) based on variants and weights from the largest genetic study in MS were calculated for each participant and assigned into deciles based on the PRS distribution in the control participants. We examined the lifetime risk for each decile and the association between PRS and MS disease variables, including age at onset and time to secondary progression.

resultsMS-PRS was calculated for 285 pwMS (mean age 53.0 ± 0.9 years, 72.3% female) and 267 control participants (mean age 51.8 ± 3.2 years, 58.1% female). Based on the lifetime risk estimation, we observed that 1:2,739 of the women with the lowest 30% genetic risk developed MS, whereas 1:92 of the women with the top 10% highest risk developed MS. For men, only 1:7,900 developed MS in the lowest 30% genetic risk group, compared with 1:293 men with the top 10% genetic risk. The PRS was not significantly associated with age at onset and time to secondary progression in both sexes. DISCUSSION: Our results show that the lifetime risk of MS is strongly influenced by genetic factors. Our findings have the potential to support diagnostic certainty in individuals with suspected MS: a high PRS could strengthen a diagnosis, but especially a PRS from the lowest tail of the PRS distribution should be considered a red flag and could prevent misdiagnosing conditions that mimic MS.

Indexed as

Genetic Predisposition to DiseaseMultifactorial InheritanceMultiple SclerosisAge of OnsetBirth CohortCohort StudiesDisease ProgressionFemaleGenetic Risk ScoreHumansMaleMiddle AgedNetherlandsRisk Factors

Identifiers

PMID39270152
PMCPMC11399064

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