Childhood obesity and multiple sclerosis: A Mendelian randomization study. (December 2021)

• Record Type: Journal Article
• Authors: Harroud, Adil; Mitchell, Ruth E; Richardson, Tom G; Morris, John A; Forgetta, Vincenzo; Davey Smith, George; Baranzini, Sergio E; Richards, J Brent
• Is Part Of: Multiple sclerosis. Volume 27:Number 14(2021)
• Page Start: 2150
• Page End: 2158
• Publication Date: 2021-12
• Subjects: Multiple sclerosis -- obesity -- Mendelian randomization -- genetic epidemiology; Central nervous system -- Diseases -- Periodicals; Myelin sheath -- Diseases -- Periodicals; Inflammation -- Periodicals; Multiple sclerosis -- Periodicals; Central Nervous System Diseases -- Periodicals; Demyelinating Diseases -- Periodicals; Inflammation -- Periodicals; Multiple Sclerosis -- Periodicals; Système nerveux central -- Maladies -- Périodiques; Gaine de myéline -- Maladies -- Périodiques; Inflammation (Pathologie) -- Périodiques; Sclérose en plaques -- Périodiques; Electronic journals; 616.834005
• DOI: 10.1177/13524585211001781
• Languages: English
• ISSNs: 1352-4585

Abstract

Background: Higher childhood body mass index (BMI) has been associated with an increased risk of multiple sclerosis (MS). 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. 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). 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. 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.