A systematic review of Mendelian randomization studies on multiple sclerosis

Fazia, Teresa; Baldrighi, Giulia Nicole; Nova, Andrea; Bernardinelli, Luisa

doi:10.1111/ejn.16088

Cited by 10 publications

(3 citation statements)

References 112 publications

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“…9 Compelling evidence also exists on the causal role-played by insufficient vitamin D levels, high body mass index (BMI), and tobacco smoking in increasing MS risk. 10…”

Section: Introductionmentioning

confidence: 99%

Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study

Nova,

Di Caprio,

Bernardinelli

et al. 2024

Mult Scler

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Background: Previous investigations into multiple sclerosis (MS) risk factors predominantly relied on retrospective studies, which do not consider different follow-up times and assume a constant risk effect throughout lifetime. Objective: We aimed to evaluate the impact of genetic and early life factors on MS diagnosis by employing a time-to-event analysis in a prospective cohort. Methods: We used the UK Biobank data, considering the observation period from birth up to 31 December 2022. We considered genetic risk, using a multiple sclerosis polygenic risk score (MS-PRS), and various early life factors. Tobacco smoking and infectious mononucleosis diagnosis were also considered as time-varying variables along the follow-up. Using a Cox proportional hazards model, we examined the associations between these factors and MS diagnosis instantaneous risk. Results: We analyzed 345,027 participants, of which 1669 had an MS diagnosis. Our analysis revealed age-dependent effects for sex (females vs males) and higher MS-PRS, with greater hazard ratios observed in young adults. Conclusion: The age-dependent effects suggest that retrospective studies could have underestimated sex and genetic variants’ risk roles during younger ages. Therefore, we emphasize the importance of a time-to-event approach using longitudinal data to better characterize age-dependent risk effects.

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“…9 Compelling evidence also exists on the causal role-played by insufficient vitamin D levels, high body mass index (BMI), and tobacco smoking in increasing MS risk. 10…”

Section: Introductionmentioning

confidence: 99%

Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study

Nova,

Di Caprio,

Bernardinelli

et al. 2024

Mult Scler

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“…MS is a chronic autoimmune disease of the central nervous system characterized by inflammation, demyelination, gliosis, and neuronal loss [ 12 , 13 ], and its onset is influenced by both genetic and environmental factors [ 9 , 10 , 11 ]. Among these, low vitamin D levels, high body mass index, previous Epstein–Barr virus (EBV) infection, and cigarette smoking have been highlighted as strong causal risk factors [ 14 , 15 , 16 ]. Moreover, several genetic variants were identified as significantly associated with MS susceptibility.…”

Section: Introductionmentioning

confidence: 99%

Multiple Sclerosis Heritability Estimation on Sardinian Ascertained Extended Families Using Bayesian Liability Threshold Model

Nova

Fazia

Saddi

et al. 2023

Genes

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Heritability studies represent an important tool to investigate the main sources of variability for complex diseases, whose etiology involves both genetics and environmental factors. In this paper, we aimed to estimate multiple sclerosis (MS) narrow-sense heritability (h2), on a liability scale, using extended families ascertained from affected probands sampled in the Sardinian province of Nuoro, Italy. We also investigated the sources of MS liability variability among shared environment effects, sex, and categorized year of birth (<1946, ≥1946). The latter can be considered a proxy for different early environmental exposures. To this aim, we implemented a Bayesian liability threshold model to obtain posterior distributions for the parameters of interest adjusting for ascertainment bias. Our analysis highlighted categorized year of birth as the main explanatory factor, explaining ~70% of MS liability variability (median value = 0.69, 95% CI: 0.64, 0.73), while h2 resulted near to 0% (median value = 0.03, 95% CI: 0.00, 0.09). By performing a year of birth-stratified analysis, we found a high h2 only in individuals born on/after 1946 (median value = 0.82, 95% CI: 0.68, 0.93), meaning that the genetic variability acquired a high explanatory role only when focusing on this subpopulation. Overall, the results obtained highlighted early environmental exposures, in the Sardinian population, as a meaningful factor involved in MS to be further investigated.

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“…On the contrary, Mendelian randomization analysis found hypovitaminosis D as a clear risk factor for developing multiple sclerosis (MS) [23].…”

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confidence: 99%

The 2023’s Growing Evidence Confirming the Relationship between Vitamin D and Autoimmune Diseases

Cutolo,

Gotelli

2023

Nutrients

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A systematic review of Mendelian randomization studies on multiple sclerosis

Cited by 10 publications

References 112 publications

Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study

Genetic and early life factors influence on time-to-multiple sclerosis diagnosis: A UK Biobank study

Multiple Sclerosis Heritability Estimation on Sardinian Ascertained Extended Families Using Bayesian Liability Threshold Model

The 2023’s Growing Evidence Confirming the Relationship between Vitamin D and Autoimmune Diseases

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