Obesity and Multiple Sclerosis: A Mendelian Randomization Study
PLOS Medicine Published: June 28, 2016http://dx.doi.org/10.1371/journal.pmed.1002053
Lauren E. Mokry , Stephanie Ross , Nicholas J. Timpson, Stephen Sawcer, George Davey Smith, J. Brent Richards
- This study just looked at genes, but suspected a vitamin D role
- Obese people need to supplement with 2.5X as much vitamin D to achieve the same blood level
- Multiple Sclerosis is more likely if low vitamin D
- So it is NOT a surprise that Obesity increases MS
See also VitaminDWiki
- Multiple Sclerosis much less likely for children who are thin and tanned - April 2017
- Genes make Multiple Sclerosis 2X more likely unless get more vitamin D - Aug 2015
- Multiple sclerosis patients have 15 ng lower levels of vitamin D – meta-analysis June 2014
- Multiple Sclerosis: number needed to treat with vitamin D may be as low as 1.3 – Meta-analysis Oct 2013
- Diseases that may be related via low vitamin D includes the following
Obesity ==> Diabetes
Obesity ==> Multiple Sclerosis
Obesity ==> Cognitive Decline
Multiple Sclerosis ==> 2.6X increased Migrane Headache, web, full text online
Multiple Sclerosis ==> 2X more Fractures, web, full text online
Multiple Sclerosis ==>>Fibromyalgia 2015
Multiple Sclerosis ==> Diabetes (T1) - Obese need 2.5X more vitamin D
Click on chart for details
Items in both of the categories of Genetics AND Obesity
- Obesity is associated with 1 to 5 poor vitamin D genes (childhood obesity in the case) – July 2024
- Obese children have poor vitamin D genes (CYP27A1, CYP2R1, CYP27B1) – March 2024
- Obese children had less gene methylation (gene not work as well) – March 2024
- Response to Vitamin D varies with genes (3,000 IU, weight loss in this RCT) – March 2022
- High-fat diet reduces CYP2R1 gene needed to make semi-activated vitamin D (mice) – Aug 2021
- Hypothesis: Obesity reduces Vitamin D production by repressing CYP2R1 gene in liver and fat tissue – July 2020
- Increased risk of weight gain when gene restricts Vitamin D getting to tissues (CYP24A1 in this case) – Nov 2019
- Obesity associated with poor Vitamin D genes (VDR in this study) – Jan 2018
- Gut genes related to important disease changed in Obese with 2,000 IU for 12 weeks – May 2019
- Obesity cut semi-activation of Vitamin D in half (mice) – Jan 2019
- Obesity might be related to Vitamin D genes – July 2018
- Vitamin D restricted in getting to cells by genes, obesity, etc – Jan 2017
- Multiple Sclerosis and obesity share some gene problems (as well as low vitamin D) – June 2016
- Vitamin D may block the obesity gene (FTO) – Jan 2014
- Vitamin D roles in obesity: genetics and cell signaling – June 2013
- Obese have 50 percent less of two enzymes in fatty tissue to process vitamin D – May 2013
- No apparent genetic association between vitamin D and obesity – Feb 2013
- Genes indicate that Obesity causes vitamin D deficiency – Feb 2013
See also web
- Prevalence of Comorbidities, Overweight and Obesity in an International Sample of People with Multiple Sclerosis and Associations with Modifiable Lifestyle Factors. PLOS Feb 2016
Full free text online - Obesity Linked To Multiple Sclerosis? MS News 2014
“. . comprehensive review analysis on the relation between obesity and autoimmune diseases, by analyzing 329 published studies.”
Download the PDF from VitaminDWiki
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.
Author Summary
Why Was This Study Done?
Multiple sclerosis (MS) is a debilitating disease that carries a large social and economic burden.
The risk factors that cause MS remain poorly understood.
Previous observational epidemiological studies have reported an association between elevated body mass index (BMI) in early adulthood and risk of MS; however, lifestyle factors that influence BMI may bias the relationship between BMI and MS.
What Did the Researchers Do and Find?
The researchers tested whether inherited genetic variation that influences BMI is associated with MS. Such analyses provide an estimate of the relationship between BMI and MS that is not influenced by confounding factors, with the exception of confounding by ancestry; since assignment to genotype at conception is a random process, it breaks associations with other potential confounding factors.
Using data from the largest genome-wide association study consortia for MS and BMI, the researchers provided evidence supporting elevated BMI as a causal risk factor for MS.
A genetically determined change in the BMI category from overweight to obese was associated with a substantially increased risk of MS in this study.
What Do These Findings Mean?
Elevated BMI could be an important, and potentially modifiable, risk factor for MS.
This provides further rationale to address rising obesity rates and to investigate whether interventions that promote a healthy lifestyle may help to mitigate MS risk.
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- “Current evidence suggests that there are several potential mechanisms through which increased BMI may affect MS risk; however, it remains unclear which of these pathways are critical. Vitamin D is a strong candidate, given that previous MR analyses demonstrate that genetically elevated BMI decreases 25-hydroxyvitamin D levels [51], and we have recently provided strong evidence supporting a causal role for reduced 25-hydroxyvitamin D levels as a risk factor for MS [30].”
- ‘In conclusion, these results provide evidence supporting a causal role for elevated BMI in MS etiology. This provides further rationale for individuals at risk for MS to maintain a healthy BMI. Whether vitamin D, or another established intermediate, is predominantly mediating this relationship warrants further investigation.