Polymorphism Analysis May Determine How Vitamin-D Levels Affect Children With Multiple Sclerosis: Presented at ANA
By Alex Morrisson
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:
- People with Multiple Sclerosis have blunted responses to Vitamin D supplementation - Jan 2024
- Get Multiple Sclerosis while younger if have a poor CYP24A1 vitamin D gene – May 2023
- Vitamin D genes increase MS relapses in children by 2X – May 2019
- CYP2R1 gene problem increases Multiple Sclerosis risk by 1.4X – Dec 2018
- Multiple Sclerosis more likely if poor vitamin D genes - 22nd study – Aug 2017
- Mendelian proof that low vitamin D (due to 3 genes) increase risk of MS by 20 percent – Nov 2016
- Autoimmune risk gene ZMIZ1 is associated with both MS and Vitamin D – Jan 2017
- Multiple Sclerosis relapse in children is twice as likely having a Vitamin D Gene score of 6 – Oct 2016
- Multiple Sclerosis and obesity share some gene problems (as well as low vitamin D) – June 2016
- Genes make Multiple Sclerosis 2X more likely unless get more vitamin D - Aug 2015
- Multiple Sclerosis is connected to Vitamin D by gene to gene interactions – Aug 2014
- Multiple Sclerosis, gene expression, and vitamin D: Venn diagrams – Aug 2014
- Epigenetics of Multiple Sclerosis – March 2014
- Increased risk of multiple sclerosis risk in African Americans due to genes – June 2013
- 98 pcnt of genes that Vitamin D activates to reduce MS are also activated by Interferon -May 2013
- Transgeneration vitamin D deficiency related to MS was found in mice – Aug 2012
- Epigenetics, vitamin D, and Multiple Sclerosis
- Learning about MS and vitamin D in offspring from mice – Sept 2011
- Vitamin D targets 4 MS genes – May 2011
- Unable to find a gene linking vitamin D and MS – March 2011
- MS and vitamin D may be related by HLA gene – March 2010
- MS due to low level of vitamin D may be due to a specific gene – July 2010
The articles in both MS and Vitamin D Receptor are:
- Poor Vitamin D Receptor increases the risk of Multiple Sclerosis in people of European descent – Feb 2024
- Multiple Sclerosis 2X-3X more likely if poor Vitamin D Receptor – Meta-analysis Feb 2020
- Risk of Multiple Sclerosis varies with the Vitamin D Receptor – meta-analysis Dec 2019
- Multiple Sclerosis and Vitamin D Receptor super enhancers – March 2019
- Vitamin D genes increase MS relapses in children by 2X – May 2019
- Immunological effects of vitamin D and their relations to autoimmunity – March 2019
- Inflammation and immune responses to Vitamin D (perhaps need to measure active vitamin D) – July 2017
- Multiple Sclerosis more likely if poor vitamin D genes - 22nd study – Aug 2017
- Multiple sclerosis (relapsing-remitting) increases activation of Vitamin D Receptor by 6.6 X – March 2017
- Multiple Sclerosis is more likely if poor Vitamin D Receptor (4X Mexico, 3X Iran)– Feb 2017
- Multiple Sclerosis much more likely if poor Vitamin D Receptor – several studies
- Multiple Sclerosis and the Vitamin D Receptor – meta-analysis July 2014
The articles in both MS and Vitamin D Binding Protein:
- Multiple Sclerosis 2.8 X more likely if poor Vitamin D Binding Protein – May 2022
- Gene variants can reduce Vitamin D response by 1.7X (14,000 IU daily, Multiple Sclerosis) – Dec 2021
- Vitamin D genes increase MS relapses in children by 2X – May 2019
- Mendelian proof that low vitamin D (due to 3 genes) increase risk of MS by 20 percent – Nov 2016
- Genes make Multiple Sclerosis 2X more likely unless get more vitamin D - Aug 2015
- Multiple Sclerosis is associated with about 1.5 X more Vitamin D Binding Protein – Jan 2015
- Late-stage MS associated with protein in spinal cord which blocks vitamin D – Jan 2013
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]