What is causing the MS pandemic?

Is it not the time to do something about the obesity pandemic? What has obesity got to do with MS? 

The latest data from Canada indicates that the prevalence and incidence of MS continues to increase; this is a trend across the world. Importantly, Canada may have just surpassed Scotland as the highest prevalence region of the world. Why is this happening? Why has MS become a pandemic? Is there anything we can do about this?

MS and other autoimmune diseases were very uncommon 150+ years ago. Our genetics haven't changed and therefore there must be an environmental factor driving the increased incidence. Could it be the macroenvironment (climate, latitude, etc.) or the microenvironment (diet, smoking, exercise, etc.)? Many of the migration and genetic studies, particularly from Canada, would argue against the microenvironment being responsible. However, I am not so sure. 

Well known non-genetic risk factors for developing MS are EBV infection, particularly late infection, low vD levels or sunlight exposure and smoking. More recent factors that have emerged are child obesity and organic solvent exposure. 

I am particularly interested in obesity, which seems to be a real risk factor as it is supported by two Mendelian randomization studies. These show that those who are genetically predisposed to being obese have a  higher risk of getting MS. What is it about obesity that raises your risk of getting MS? Is it because adipose tissue is pro-inflammatory and stimulates autoimmunity secondarily? Could adipose tissue soak up circulating vD as it is a fat-soluble vitamin and lower vD levels? Or could obesity be the smoking gun and represent something in our diets that have triggered the epidemic? These are only a few of the hypotheses floating about amongst academic who think MS is a preventable disease. 

As always these observations are associations and not causal. To prove obesity is in the causal pathway will be a gargantuan task. But linking obesity to an increasing incidence of MS and other autoimmune diseases may help public health officials and politician do something about the obesity pandemic that threatens the planet. 

Multiple sclerosis: Prevalence and impact. The Daily, Wednesday, January 17, 2018.

Estimates from individual provinces suggest that the prevalence of multiple sclerosis (MS) among Canadians may be one of the highest in the world. A new study released today in the publication Health Reports provides information on the impact MS has on people's lives, such as mobility, pain, sleep and cognition. About two-thirds of those diagnosed reported that their lives were affected moderately, quite a bit, or extremely by MS. Although 57% of people with MS could walk without aid, almost one-third (31%) required a wheelchair, a mechanical aid such as a cane or walker, or the help of another person, and 12% could not walk at all. Just over half (53%) were usually pain-free, with the rest reporting pain that prevented a few activities (21%) or some/most activities (25%). Close to two-thirds (62%) experienced difficulty getting a good night's sleep. Half (50%) of people whose only neurological condition was MS had difficulty remembering most things and/or thinking and solving problems. MS can be limiting in other ways. Close to one-third reported that it had prevented them from driving (30%), or compromised their educational opportunities (32%). More than half (58%) experienced at least some limitations in job opportunities. As well, 43% reported that MS had a negative impact on their social interactions, such as feeling left out, embarrassed, or that others felt uncomfortable around them or avoided them. This study also provides the most recent national prevalence estimates of MS. An estimated 93,500 Canadians living in private households and 3,800 in long-term care institutions reported a diagnosis of MS. At 290 cases per 100,000 in the household population, prevalence exceeded that in many other countries and was higher than reported in earlier Canadian studies. Women are two to three times more likely than men to have MS (2.6 women reported MS for every man with the condition). Unlike neurological disorders such as dementia and Parkinson's disease that tend to develop at older ages, MS is more prevalent in younger adults. MS was diagnosed between the ages of 20 and 49 for 82% of those with the disorder.

Mokry et al. Obesity and Multiple Sclerosis: A Mendelian Randomization Study. PLoS Med. 2016 Jun 28;13(6):e1002053.

BACKGROUND: Observational studies have reported an association between obesity, as measured by elevated body mass index (BMI), in early adulthood and risk of multiple sclerosis (MS). However, bias potentially introduced by confounding and reverse causation may have influenced these findings. Therefore, we elected to perform Mendelian randomization (MR) analyses to evaluate whether genetically increased BMI is associated with an increased risk of MS.

METHODS AND FINDINGS: Employing a two-sample MR approach, we used summary statistics from the Genetic Investigation of Anthropometric Traits (GIANT) consortium and the International MS Genetics Consortium (IMSGC), the largest genome-wide association studies for BMI and MS, respectively (GIANT: n = 322,105; IMSGC: n = 14,498 cases and 24,091 controls). Seventy single nucleotide polymorphisms (SNPs) were genome-wide significant (p < 5 x 10-8) for BMI in GIANT (n = 322,105) and were investigated for their association with MS risk in the IMSGC. The effect of each SNP on MS was weighted by its effect on BMI, and estimates were pooled to provide a summary measure for the effect of increased BMI upon risk of MS. Our results suggest that increased BMI influences MS susceptibility, where a 1 standard deviation increase in genetically determined BMI (kg/m2) increased odds of MS by 41% (odds ratio [OR]: 1.41, 95% CI 1.20-1.66, p = 2.7 x 10-5, I2 = 0%, 95% CI 0-29). Sensitivity analyses, including MR-Egger regression, and the weighted median approach provided no evidence of pleiotropic effects. The main study limitations are that, while these sensitivity analyses reduce the possibility that pleiotropy influenced our results, residual pleiotropy is difficult to exclude entirely.

CONCLUSION: Genetically elevated BMI is associated with risk of MS, providing evidence for a causal role for obesity in MS etiology. While obesity has been associated with many late-life outcomes, these findings suggest an important consequence of childhood and/or early adulthood obesity.

Gianfrancesco et al. Causal Effect of Genetic Variants Associated With Body Mass Index on Multiple Sclerosis Susceptibility. Am J Epidemiol. 2017 Feb 1;185(3):162-171.

Multiple sclerosis (MS) is an autoimmune disease with both genetic and environmental risk factors. Recent studies indicate that childhood and adolescent obesity double the risk of MS, but this association may reflect unmeasured confounders rather than causal effects of obesity. We used separate-sample Mendelianrandomization to estimate the causal effect of body mass index (BMI) on susceptibility to MS. Using data from non-Hispanic white members of the Kaiser Permanente Medical Care Plan of Northern California (KPNC) (2006-2014; 1,104 cases of MS and 10,536 controls) and a replication data set from Sweden (the Epidemiological Investigation of MS (EIMS) and the Genes and Environment in MS (GEMS) studies, 2005-2013; 5,133 MS cases and 4,718 controls), we constructed a weighted genetic risk score using 97 variants previously established to predict BMI. Results were adjusted for birth year, sex, education, smoking status, ancestry, and genetic predictors of MS. Estimates in KPNC and Swedish data sets suggested that higher genetically induced BMI predicted greater susceptibility to MS (odds ratio = 1.13, 95% confidence interval: 1.04, 1.22 for the KPNC sample; odds ratio = 1.09, 95% confidence interval: 1.03, 1.15 for the Swedish sample). Although the mechanism remains unclear, to our knowledge, these findings support a causal effect of increased BMI on susceptibility to MS for the first time, and they suggest a role for inflammatory pathways that characterize both obesity and the MS disease process.


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