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Multiple Sclerosis relapse in children is twice as likely having a Vitamin D Gene score of 6 – Oct 2016

Polymorphism Analysis May Determine How Vitamin-D Levels Affect Children With Multiple Sclerosis: Presented at ANA

By Alex Morrisson

VitaminDWiki

I have not seen a genetic risk score before this paper
Genetic Risk score =6

  • reduced measured vitamin D levels by 15 ng
  • increased risk of MS relapse by 1.94

This ignores any increased risk of gene problems which are downstream from the vitamin D test
The articles in both MS and Genetics are:

The articles in both MS and Vitamin D Receptor are:

The articles in both MS and Vitamin D Binding Protein:


BALTIMORE, Maryland — October 19, 2016 — Relapses among paediatric patients with multiple sclerosis appear to occur almost twice as frequently if those patients have a genetic disposition to low Vitamin-D levels compared with those who do not have those polymorphisms, according to researchers at the 141st Annual Meeting of the American Neurological Association (ANA).

Jennifer Graves, MD, PhD, University of California at San Francisco, San Francisco, California, and colleagues created a Vitamin D Genetic Risk Score to analyse outcomes if a person has high levels of single nucleotide polymorphisms (SNPs) in their serum that are associated with Vitamin-D levels.

If a person had 6 units on the Genetic Risk Score, there is a 94% increase in the hazard ratio (HR, 1.94) for relapse (95% confidence interval CI 1.19 to 3.15, P = .0007), said Dr. Graves, speaking here at a poster presentation on October 16.

“A risk score of 3 of these SNPS with independent effects was normally distributed and explained 13% of the variance of Vitamin-D level in these subjects,” Dr. Graves explained. “These findings support a causal association of Vitamin D with relapse rate.”

“Six units of the Vitamin D Genetic Risk Score, comparing highest to lowest scores, was associated with a 14.9 ng/ml lower Vitamin-D level (P = .0000052),” she said. “This is quite remarkable. Even in a sample size of 181 children, we have reached almost genome-level significance.”

The effect size was nearly identical in a 110-patient replication cohort that did not include any of the children in the 181-patient discovery set.

Dr. Graves and colleagues developed the Genetic Risk Score by assigning values to the SNPs, which, in the literature, are associated with Vitamin-D levels. The 3 independent SNP alleles were identified as rs7041, rs909217 and rs2276360.

“Our project was to look at the genetic drivers of Vitamin D levels — the polymorphisms that are associated with serum Vitamin-D levels,” Dr. Graves noted. “These are things that you are born with.”

To create the Vitamin-D genetic risk score, the research team typed DNA samples from 181 paediatric patients with multiple sclerosis for 29 functional polymorphisms in Vitamin-D pathway genes, identified through the literature to be associated with 25-hydroxy Vitamin D levels in human subjects. Through regression modelling, the researchers determined that 6 of the SNPs were strongly associated with Vitamin-D levels in the paediatric patients with multiple sclerosis.

Dr. Graves and colleagues continue to determine whether the association with relapses can be confirmed, pending accumulation of additional patients and follow-up time in the second cohort.

The results of this study do not reveal whether supplementation with Vitamin D in the patients with a high genetic risk score will reduce relapses. In ongoing studies with Vitamin D, however, DNA material is being collected to help determine the answer to the question of how patients respond to therapy based on their genotype.

The patients in the discovery set of this study were approximately 13 years old, and 66% were female. Median follow-up was about 34 months, and the patients averaged about 1 relapse/year. Around 65% of the cohort was white; another 30% of the patients were Hispanic. Baseline median 25-hydroxy Vitamin D was 23 ng/ml.

[Presentation title: Vitamin D Genetic Risk Score Is Strongly Associated with Vitamin D Levels and Relapse Rate in Pediatric MS Patients. Abstract S109]

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