| Title: | Childhood obesity and multiple sclerosis: A Mendelian randomization study |
| Journal: | Multiple Sclerosis Journal |
| Published: | 22 Mar 2021 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/33749377/ |
| DOI: | https://doi.org/10.1177/13524585211001781 |
| URL: | https://research-information.bris.ac.uk/files/270942962/RevMC_ChObes_MSJ_012620.pdf |
| Citations: | 34 (22 in last 2 years) as of 8 Aug 2024 |
Publication 4481
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Abstract
BACKGROUND: Higher childhood body mass index (BMI) has been associated with an increased risk of multiple sclerosis (MS).</p>
OBJECTIVE: To evaluate whether childhood BMI has a causal influence on MS, and whether this putative effect is independent from early adult obesity and pubertal timing.</p>
METHODS: We performed Mendelian randomization (MR) using summary genetic data on 14,802 MS cases and 26,703 controls. Large-scale genome-wide association studies provided estimates for BMI in childhood (n = 47,541) and adulthood (n = 322,154). In multivariable MR, we examined the direct effects of each timepoint and further adjusted for age at puberty. Findings were replicated using the UK Biobank (n = 453,169).</p>
RESULTS: Higher genetically predicted childhood BMI was associated with increased odds of MS (odds ratio (OR) = 1.26/SD BMI increase, 95% confidence interval (CI): 1.07-1.50). However, there was little evidence of a direct effect after adjusting for adult BMI (OR = 1.03, 95% CI: 0.70-1.53). Conversely, the effect of adult BMI persisted independent of childhood BMI (OR = 1.43; 95% CI: 1.01-2.03). The addition of age at puberty did not alter the findings. UK Biobank analyses showed consistent results. Sensitivity analyses provided no evidence of pleiotropy.</p>
CONCLUSION: Genetic evidence supports an association between childhood obesity and MS susceptibility, mediated by persistence of obesity into early adulthood but independent of pubertal timing.</p>
9 Keywords
- Adult
- Body Mass Index
- Child
- Genome-Wide Association Study
- Humans
- Mendelian Randomization Analysis
- Multiple Sclerosis
- Pediatric Obesity
- Polymorphism, Single Nucleotide
8 Authors
- Adil Harroud
- Ruth E Mitchell
- Tom G Richardson
- John A Morris
- Vincenzo Forgetta
- George Davey Smith
- Sergio E Baranzini
- J Brent Richards
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