Effects of Vitamin D and Body Mass Index on Disease Risk and Relapse Hazard in Multiple Sclerosis

Abstract

Background and ObjectivesDecreased vitamin D levels and obesity are associated with an increased risk for multiple sclerosis (MS). However, whether they also affect the disease course after onset remains unclear. With larger data sets now available, we used Mendelian randomization (MR) to determine whether serum 25-hydroxyvitamin D (25OHD) and body mass index (BMI) are causally associated with MS risk and, moving beyond susceptibility toward heterogeneity, with relapse hazard.MethodsWe used genetic variants from 4 distinct genome-wide association studies (GWASs) for serum 25OHD in up to 416,247 individuals and for BMI from a GWAS in 681,275 individuals. Applying 2-sample MR, we examined associations of 25OHD and BMI with the risk of MS, with summary statistics from the International Multiple Sclerosis Genetics Consortium GWAS in 14,802 MS cases and 26,703 controls. In addition, we examined associations with relapse hazard, with data from our GWAS in 506 MS cases.ResultsA 1-SD increase in genetically predicted natural-log transformed 25OHD levels decreased odds of MS up to 28% (95% CI: 12%–40%, p = 0.001) and decreased hazard for a relapse occurring up to 43% (95% CI: 15%–61%, p = 0.006). A 1-SD increase in genetically predicted BMI, corresponding to roughly 5 kg/m2, increased risk for MS with 30% (95% CI: 15%–47%, p = 3.76 × 10−5). On the contrary, we did not find evidence for a causal role of higher BMI with an increased hazard for occurrence of a relapse.DiscussionThis study supports causal effects of genetically predicted serum 25OHD concentrations and BMI on risk of MS. In contrast, serum 25OHD but not BMI is significantly associated with relapse hazard after onset. These findings might offer clinical implications for both prevention and treatment.

Association of Vitamin D Polygenic Risk Scores and Disease Outcome in People With Multiple Sclerosis

“…The authors reported a protective effect of 25(OH)D PGS regarding relapse hazard. 28 In our study, an association between 25(OH)D PGS and clinical relapses was not observed, although we included a larger sample size and more diverse set of MS outcomes. This remained true when numerous other clinical and radiologic outcomes were considered as potentially more sensitive proxies of disease activity.…”

“… 50 We also performed sensitivity analyses to confirm consistent results were observed when applying Mendelian randomization (MR); this approach was previously applied in a study linking 25(OH)D and relapse hazard. 28 To select instrumental variables (IVs) for 25(OH)D, we used the set of summary statistics for 25(OH)D used to create 25(OH)D PGS for our primary analyses and we aligned alleles to ensure directionality of effect estimates was maintained. 20 We clumped 25(OH)D variants using a p -value threshold of 5e-8, distance of 10,000 kilobases, and LD of 0.001.…”

“… 27 Although a possible association between genetically determined 25(OH)D levels and relapse risk was noted in a Belgian cohort of people with MS (PwMS), this study involved a single center and did not consider other clinical outcomes or objective imaging outcomes such as the rate of new lesion development, which has a strong body of support from observational studies. 28 Thus, to address this gap, we explored whether genetically determined 25(OH)D levels are associated with disease outcomes in a large, multinational study of PwMS considering multiple radiologic and clinical outcomes. We hypothesized that genetically predicted higher 25(OH)D levels would be associated with better MS outcomes over time.…”

The immunomodulatory phenomenon of vitamin D in the pathogenesis of Multiple Sclerosis

“…Dodatni gradient szerokości geograficznej w rozpowszechnieniu i zapadalności na stwardnienie rozsiane, przypisywany częściowo wpływowi witaminy D i ekspozycji napromienie słoneczne, ustala się we wczesnym okresie życia. [56,57,58] Istotnym aspektem są równieżmigracje. Szerokość geograficzna jest powiązana z wieloma czynnikami fizycznymi, chemicznymi, biologicznymi i społecznymi, ale najsilniejskorelowana jest z czasem trwania i intensywnością światła słonecznego [10,41].Wzrost ryzyka SM jest największy, gdy migracja następuje w dzieciństwie [6,54,55].…”

The role of constitutional features of body structure in the occurrence and course of multiple sclerosis (literature review)

“…Дослідники не знайшли зв'язку показників індексу маси тіла, які перевищують норму із підвищеним ризиком виникнення рецидиву. Так зниження рівня вітаміну D у порівнянні з нормою та ожиріння пов'язані з високим ризиком розвитку розсіяного склерозу [28].…”