Age-specific effects of childhood body mass index on multiple sclerosis risk

• Published in: Journal of neurology Vol. 269; no. 9; pp. 5052 - 5060
• Main Authors: Hone, Luke, Jacobs, Benjamin M., Marshall, Charles, Giovannoni, Gavin, Noyce, Alastair, Dobson, Ruth
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2022; Springer Nature B.V
• Subjects: Age; Age Factors; Birth; Body Mass Index; Child; Child, Preschool; Childhood; Children; Genome-wide association studies; Genome-Wide Association Study; Genomes; Humans; Infant; Medicine; Medicine & Public Health; Mendelian Randomization Analysis; Multiple sclerosis; Multiple Sclerosis - epidemiology; Multiple Sclerosis - genetics; Neurology; Neuroradiology; Neurosciences; Original Communication; Polymorphism, Single Nucleotide; Risk factors; Sensitivity analysis; Single-nucleotide polymorphism; Body mass index; Multiple sclerosis; Mendelian randomization; Epidemiology; Causation
• ISSN: 0340-5354; 1432-1459; 1432-1459
• DOI: 10.1007/s00415-022-11161-4

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 (N SNPs ) = 7, p  = 0.39], Infancy (OR 1.18, 95% CI 1.04–1.33, N SNPs  = 18, p  = 0.01), Early childhood (OR 1.31, 95% CI 1.03–1.66, N SNPs  = 4, p  = 0.03), Later childhood (OR 1.34, 95% CI 1.08–1.66, N SNPs  = 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.