J Neurol. 2022 May 9. doi: 10.1007/s00415-022-11161-4. Online ahead of print.
ABSTRACT
OBJECTIVE: Higher body mass index (BMI) during early life is thought to be a causal risk factor for multiple sclerosis (MS). We used longitudinal Mendelian randomisation (MR) to determine whether there is a critical window during which BMI influences MS risk.
METHODS: Summary statistics for childhood BMI (n ~ 28,000 children) and for MS susceptibility were obtained from recent large genome-wide association studies (GWAS) (n = 14,802 MS, 26,703 controls). We generated exposure instruments for BMI during four non-overlapping age epochs (< 3 months, 3 months-1.5 years, 2-5 years, and 7-8 years) and performed MR using the inverse variance weighted method with standard sensitivity analyses. Multivariable MR was used to account for effects mediated via later-life BMI.
RESULTS: For all age epochs other than birth, genetically determined higher BMI was associated with an increased liability to MS: Birth [Odds Ratio (OR) 0.81, 95% Confidence Interval (CI) 0.50-1.31, Number of Single-Nucleotide Polymorphisms (NSNPs) = 7, p = 0.39], Infancy (OR 1.18, 95% CI 1.04-1.33, NSNPs = 18, p = 0.01), Early childhood (OR 1.31, 95% CI 1.03-1.66, NSNPs = 4, p = 0.03), Later childhood (OR 1.34, 95% CI 1.08-1.66, NSNPs = 4, p = 0.01). Multivariable MR suggested that these effects may be mediated by effects on adult BMI.
CONCLUSION: We provide evidence using MR that genetically determined higher BMI during early life is associated with increased MS risk. This effect may be driven by shared genetic architecture with later-life BMI.
PMID:35532785 | DOI:10.1007/s00415-022-11161-4
