Childhood obesity and multiple sclerosis: A Mendelian randomization study

Harroud, Adil; Mitchell, Ruth; Richardson, Tom G; Morris, John; Forgetta, Vincenzo; Smith, George Davey; Baranzini, Sergio E.; Richards, J. Brent

doi:10.1177/13524585211001781

Cited by 42 publications

(31 citation statements)

References 40 publications

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“…One of the most recent research studies on the topic is the Mendelian randomization study conducted by (Harroud et al, 2021). Including large cohorts of MS and control cases, authors showed that higher childhood BMI is associated with agreater risk of MS, independent of age at puberty [ 14 ]. Thus, besides environmental factors, genetic evidence also confirms the influence of childhood obesity on MS susceptibility.…”

Section: Obesity As An Environmental Risk Factor In Multiple Sclerosismentioning

confidence: 99%

Obesity and Multiple Sclerosis—A Multifaceted Association

Schreiner

Genes

2021

JCM

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Background: Given the common elements in the pathophysiological theories that try to explain the appearance and evolution of obesity and multiple sclerosis, the association between the two pathologies has become an increasingly researched topic in recent years. On the one hand, there is the chronic demyelinating inflammation caused by the autoimmune cascade of multiple sclerosis, while on the other hand, according to the latest research, it has been shown that obesity shares an inflammatory component with most chronic diseases. Methods: The authors performed independent research of the available literature in the most important electronic databases (PubMed, Google Scholar, Embase, and Science Direct) in February 2021. After applying the exclusion criteria, the reviewers focused on the most relevant articles published during the last 10 years with respect to epidemiology and pathophysiology. Results: The data presented are a step forward in trying to elucidate the intricate relationship between obesity and MS, especially the causal relationship between childhood and adolescent obesity and MS, focusing on the epidemiological associations observed in the most relevant observational studies conducted in recent years. In the second part, the authors comment on the latest findings related to the pathophysiological mechanisms that may explain the correlations between obesity and multiple sclerosis, focusing also on the role of adipokines. Conclusions: Based on available epidemiological data, obesity in early life appears to be strongly associated with a higher risk of MS development, independent of other risk factors. Although much research has been done on the pathophysiology of obesity, MS, their possible common mechanism, and the role of adipokines, further studies are needed in order to explain what remains unknown. No relevant data were found regarding the association between obesity, disability (high EDSS score), and mortality risk in MS patients. Thus, we consider that this topic should be elucidated in future research.

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Section: Obesity As An Environmental Risk Factor In Multiple Sclerosismentioning

confidence: 99%

Obesity and Multiple Sclerosis—A Multifaceted Association

Schreiner

Genes

2021

JCM

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“…Observational data supports the concept that BMI during adolescence, particularly late teenage years, is a risk factor for MS 4,7,9,18 . Mendelian randomisation studies have strengthened the notion that this may be a causal relationship 5,6 . It remains debatable whether childhood BMI is a causal risk factor for MS independently of its persistence into adolescence/adulthood, or whether it purely affects MS risk via its strong correlation with BMI in early adult life.…”

Section: Discussionmentioning

confidence: 99%

“…It remains debatable whether childhood BMI is a causal risk factor for MS independently of its persistence into adolescence/adulthood, or whether it purely affects MS risk via its strong correlation with BMI in early adult life. In favour of the latter, a recent study used multivariable MR to regress out the effects of genetic instruments for childhood BMI mediated via adult BMI: controlling for the effect of adult BMI abolished the observed MR effect of childhood BMI on MS risk, suggesting that persistently raised BMI into adulthood, rather than transiently increased BMI during childhood, is the causal risk factor 6 . These results, obtained with larger datasets for early life BMI, suggest that what we observe may be driven by the same phenomenon - pleiotropic SNPs acting on MS risk via their effect on BMI in later life rather than in childhood per se .…”

Section: Discussionmentioning

confidence: 99%

“…Mendelian Randomisation (MR) is a type of instrumental variable (IV) analysis that uses genetic variants as proxies to examine whether observed associations between an exposure and an outcome are likely to be causal 2,3 . Childhood obesity has been identified as a potential causal MS risk factor in both epidemiological 4,5 and MR studies 5–7 . A consistent finding is that birth weight is not associated with MS risk, whereas higher BMI during later childhood and adolescence appears to be a risk factor 4,7–9 .…”

Section: Introductionmentioning

confidence: 99%

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Age-specific effects of childhood Body Mass Index on multiple sclerosis risk

Hone

Jacobs

Marshall

et al. 2021

Preprint

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Objective Higher childhood 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 and for MS susceptibility were obtained from recent large GWAS. We generated exposure instruments for BMI during four non-overlapping 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. Results At all time epochs other than birth, genetically-elevated BMI was associated with an increased liability to MS: Birth (OR 0.81, 95%CI 0.50-1.31, 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). There was no evidence that horizontal pleiotropy was biasing the IVW estimates at any of these points. There was evidence of an upwards trend in MS risk from birth to 8 years (Mann-Kendall test, tau = 0.636, 2-sided p-value =0.005). Conclusion We provide novel evidence using longitudinal MR that genetically-determined higher BMI during early life (from 3 months) increases MS risk, and that the magnitude of this effect increases towards late childhood and adolescence.

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“…The growing world-wide obesity epidemic has multiple deleterious effects on public health and has also been associated with an increased risk of MS [46]. Increased obesity leads to lower levels of 25-hydroxyvitamin D which in turn predisposes to MS [47]. The association between obesity and MS is similar among men and women, and the observed trend of higher BMI resulted in a higher risk of developing MS [48].…”

Section: Discussionmentioning

confidence: 99%

Multiple sclerosis incidence rate in southern Iran: a Bayesian epidemiological study

et al. 2021

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Background Multiple Sclerosis (MS) remains to be a public health challenge, due to its unknown biological mechanisms and clinical impacts on young people. The prevalence of this disease in Iran is reported to be 5.30 to 74.28 per 100,000-person. Because of high prevalence of this disease in Fars province, the purpose of this study was to assess the spatial pattern of MS incidence rate by modeling both the associations s of spatial dependence between neighboring regions and risk factors in a Bayesian Poisson model, which can lead to the improvement of health resource allocation decisions. Method Data from 5468 patients diagnosed with MS were collected, according to the McDonald’s criteria. New cases of MS were reported by the MS Society of Fars province from 1991 until 2016. The association between the percentage of people with low vitamin D intake, smoking, abnormal BMI and alcohol consumption in addition to spatial structure in a Bayesian spatio-temporal hierarchical model were used to determine the relative risk and trend of MS incidence rate in 29 counties of Fars province. Results County-level crude incidence rates ranged from 0.22 to 11.31 cases per 100,000-person population. The highest relative risk was estimated at 1.80 in the county of Shiraz, the capital of Fars province, while the lowest relative risk was estimated at 0.11 in Zarindasht county in southern of Fars. The percentages of vitamin D supplementation intake and smoking were significantly associated with the incidence rate of MS. The results showed that 1% increase in vitamin D supplementation intake is associated with 2% decrease in the risk of MS and 1% increase in smoking is associated with 16% increase in the risk of MS. Conclusion Bayesian spatio-temporal analysis of MS incidence rate revealed that the trend in the south and south east of Fars province is less steep than the mean trend of this disease. The lower incidence rate was associated with a higher percentage of vitamin D supplementation intake and a lower percentage of smoking. Previous studies have also shown that smoking and low vitamin D, among all covariates or risk factors, might be associated with high incidence of MS.

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Childhood obesity and multiple sclerosis: A Mendelian randomization study

Cited by 42 publications

References 40 publications

Obesity and Multiple Sclerosis—A Multifaceted Association

Obesity and Multiple Sclerosis—A Multifaceted Association

Age-specific effects of childhood Body Mass Index on multiple sclerosis risk

Multiple sclerosis incidence rate in southern Iran: a Bayesian epidemiological study

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