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Childhood obesity and multiple sclerosis: A Mendelian randomization study.

Adil Harroud1, Ruth E Mitchell2, Tom G Richardson2

  • 1Department of Neurology, University of California San Francisco, San Francisco, CA, USA/Weill Institute for Neurosciences, University of California San Francisco, San Francisco, CA, USA/Centre for Clinical Epidemiology, Department of Epidemiology, Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada.

Multiple Sclerosis (Houndmills, Basingstoke, England)
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Childhood obesity increases multiple sclerosis (MS) risk, with this effect primarily driven by obesity persisting into adulthood. Pubertal timing does not appear to influence this association.

Keywords:
Mendelian randomizationMultiple sclerosisgenetic epidemiologyobesity

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Area of Science:

  • Epidemiology
  • Genetics
  • Neurology

Background:

  • Higher childhood body mass index (BMI) is linked to increased multiple sclerosis (MS) risk.
  • Investigating the causal relationship between childhood BMI and MS is crucial for understanding disease etiology.

Purpose of the Study:

  • To determine if childhood BMI causally influences MS risk.
  • To assess if this effect is independent of adult obesity and pubertal timing.

Main Methods:

  • Mendelian randomization (MR) analysis using genetic data from MS cases and controls.
  • Genome-wide association studies (GWAS) for childhood and adult BMI.
  • Multivariable MR and replication in UK Biobank data.

Main Results:

  • Genetically predicted childhood BMI was associated with higher MS odds (OR=1.26 per SD).
  • This association diminished after adjusting for adult BMI, suggesting mediation by adult obesity.
  • Adult BMI independently predicted MS risk (OR=1.43), irrespective of childhood BMI.

Conclusions:

  • Genetic evidence supports a link between childhood obesity and MS susceptibility.
  • The effect is mediated by the persistence of obesity into early adulthood.
  • Pubertal timing does not significantly modify the association between BMI and MS risk.