Evidence map›Paper›PMID 27351487›Full record

ArticlePLoS medicine2016

Obesity and Multiple Sclerosis: A Mendelian Randomization Study.

Lauren E Mokry, Stephanie Ross, Nicholas J Timpson, Stephen Sawcer, George Davey Smith, J Brent Richards

Open access · goldAbstract read
In one paragraph

Article in PLoS medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 132 papers, 7 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
132citing papers in PubMed, 7 pooled it
18.4field-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

132 citing papers in PubMed, 7 syntheses or guidelines pooled it, 261 citations in OpenAlex.

  1. Guideline
  2. Pooled it
  3. Pooled it
  4. Relationships between accelerometer-measured and multiple sclerosis: a 2-sample Mendelian randomization study.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2021
    Pooled it
  5. Pooled it
  6. Type 2 Diabetes: How Much of an Autoimmune Disease?Frontiers in endocrinology · 2019
    Pooled it
  7. Pooled it
  8. Article
  9. Article
  10. Review
  11. Review
  12. Is Obesity a Modifiable Risk Factor in Multiple Sclerosis? Mechanistic Insights into Neuroinflammation and Oxidative Damage.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026
    Review
  13. Article
  14. Observational
  15. Article
  16. 3D Bioprinting Strategies in Autoimmune Disease Models.International journal of molecular sciences · 2025
    Review
  17. Review
  18. Article
  19. Article
  20. Article

72 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 2 countries.

Lauren E MokryDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
Stephanie RossCentre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montreal, Quebec, Canada.
Nicholas J TimpsonMRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.ORCID 0000-0002-7141-9189
Stephen SawcerDepartment of Clinical Neurosciences, Cambridge Biomedical Campus, Cambridge, United Kingdom.ORCID 0000-0001-7685-0974
George Davey SmithMRC Integrative Epidemiology Unit, School of Social and Community Medicine, University of Bristol, Bristol, United Kingdom.
J Brent RichardsDepartment of Epidemiology, Biostatistics and Occupational Health, McGill University, Montreal, Quebec, Canada.
Jewish General Hospital · CAUniversity of Bristol · GBKing's College London · GB

Funding

CIHRDepartment of HealthMedical Research Council MC_UU_12013/1Medical Research Council MC_UU_12013/3Wellcome Trust 202802/Z/16/Z
6 · The paper itself

Abstract

backgroundObservational studies have reported an association between obesity, as measured by elevated body mass index (BMI), in early adulthood and risk of multiple sclerosis (MS). However, bias potentially introduced by confounding and reverse causation may have influenced these findings. Therefore, we elected to perform Mendelian randomization (MR) analyses to evaluate whether genetically increased BMI is associated with an increased risk of MS. METHODS AND

findingsEmploying a two-sample MR approach, we used summary statistics from the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the International MS Genetics Consortium (IMSGC), the largest genome-wide association studies for BMI and MS, respectively (GIANT: n = 322,105; IMSGC: n = 14,498 cases and 24,091 controls). Seventy single nucleotide polymorphisms (SNPs) were genome-wide significant (p < 5 x 10-8) for BMI in GIANT (n = 322,105) and were investigated for their association with MS risk in the IMSGC. The effect of each SNP on MS was weighted by its effect on BMI, and estimates were pooled to provide a summary measure for the effect of increased BMI upon risk of MS. Our results suggest that increased BMI influences MS susceptibility, where a 1 standard deviation increase in genetically determined BMI (kg/m2) increased odds of MS by 41% (odds ratio [OR]: 1.41, 95% CI 1.20-1.66, p = 2.7 x 10-5, I2 = 0%, 95% CI 0-29). Sensitivity analyses, including MR-Egger regression, and the weighted median approach provided no evidence of pleiotropic effects. The main study limitations are that, while these sensitivity analyses reduce the possibility that pleiotropy influenced our results, residual pleiotropy is difficult to exclude entirely.

conclusionGenetically elevated BMI is associated with risk of MS, providing evidence for a causal role for obesity in MS etiology. While obesity has been associated with many late-life outcomes, these findings suggest an important consequence of childhood and/or early adulthood obesity.

Indexed as

Mendelian Randomization AnalysisBody Mass IndexGenome-Wide Association StudyHumansMultiple SclerosisObesityOdds RatioPolymorphism, Single Nucleotide

Identifiers

PMID27351487
PMCPMC4924848
OpenAlexW2465687223

What OpenQuestion 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 OpenQuestion graph.