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Poor Vitamin D Receptor increases the risk of Multiple Sclerosis in people of European descent – Feb 2024


Evidence supports a causal association between allele-specific vitamin D receptor binding and multiple sclerosis among Europeans

PNAS 121 (8) https://doi.org/10.1073/pnas.2302259121 PDF is behind a paywall
Cameron Adams, Ali Manouchehrinia, Hong L. Quach, +6, and Lisa F. Barcellos lbarcellos at berkeley.edu

There is evidence for a causal association between 25-hydroxyvitamin D (25(OH)D) serum levels and multiple sclerosis (MS), but the underlying mechanisms are unknown. We conducted a Mendelian Randomization study to estimate causal associations between vitamin D receptor (VDR) binding at a locus and MS susceptibility using genetic instrumental variables constructed from variants previously associated with allele-specific VDR-binding (VDR-binding variant; VDR-BV) and serum 25(OH)D. Two VDR-BV (rs2881514; rs2531804) were independently associated with MS and rs2881514 demonstrated significant interaction with 25(OH)D, providing evidence for a causal association between rs2881514 and MS. Our results demonstrate that genetic variation in individual VDR binding sites contributes to MS and are relevant to other autoimmune diseases for which a role for vitamin D has been implicated.

Abstract
Although evidence exists for a causal association between 25-hydroxyvitamin D (25(OH)D) serum levels, and multiple sclerosis (MS), the role of variation in vitamin D receptor (VDR) binding in MS is unknown. Here, we leveraged previously identified variants associated with allele imbalance in VDR binding (VDR-binding variant; VDR-BV) in ChIP-exo data from calcitriol-stimulated lymphoblastoid cell lines and 25(OH)D serum levels from genome-wide association studies to construct genetic instrumental variables (GIVs). GIVs are composed of one or more genetic variants that serve as proxies for exposures of interest. Here, GIVs for both VDR-BVs and 25(OH)D were used in a two-sample Mendelian Randomization study to investigate the relationship between VDR binding at a locus, 25(OH)D serum levels, and MS risk. Data for 13,598 MS cases and 38,887 controls of European ancestry from Kaiser Permanente Northern California, Swedish MS studies, and the UK Biobank were included. We estimated the association between each VDR-BV GIV and MS. Significant interaction between a VDR-BV GIV and a GIV for serum 25OH(D) was evidence for a causal association between VDR-BVs and MS unbiased by pleiotropy. We observed evidence for associations between two VDR-BVs (rs2881514, rs2531804) and MS after correction for multiple tests. There was evidence of interaction between rs2881514 and a 25(OH)D GIV, providing evidence of a causal association between rs2881514 and MS. This study is the first to demonstrate evidence that variation in VDR binding at a locus contributes to MS risk. Our results are relevant to other autoimmune diseases in which vitamin D plays a role.


VitaminDWiki - 14 studies in both categories MS and VDR

This list is automatically updated


VitaminDWiki – Overview MS and vitamin D contains

Clinical interventions have shown that Vitamin D can prevent, treat, and even cure Multiple Sclerosis, at a tiny fraction of the cost of the drugs now used to treat it, and without side effects.

Summary: lack of consensus on how much to prevent, treat, or cure MS.


VitaminDWiki – Multiple Sclerosis 32 percent less likely among those with more than 32 ng of vitamin D – Dec 2019

UV and Sunshine reduces MS risk

Other things also help

High Dose Vitamin D and cofactors

Number of MS studies which are also in other categories

  • 22 studies in Genetics - genes can restrict Vitamin D getting to the blood and to the cells
  • 14 studies in Vitamin D Receptor - gene which restricts D from getting to the cells
  • 7 studies in Vitamin D Binding Protein - gene which restricts D from getting to the cells
  • 21 studies in Ultraviolet light - may be even better than Vitamin D in preventing and treating MS
  • 9 studies in Omega-3 - which helps Vitamin D prevent and treat MS

VitaminDWiki – Vitamin D Receptor is associated in over 58 autoimmune studies


VitaminDWiki - The risk of 50+ diseases at least double with poor Vitamin D Receptor


VitaminDWiki - Vitamin D Receptor activation can be increased in many ways

Resveratrol,  Omega-3,  MagnesiumZinc,   Quercetin,   non-daily Vit D,  Curcumin,   Berberine,  intense exercise, Butyrate   Sulforaphane   Ginger,   Essential oils, etc  Note: The founder of VitaminDWiki uses 10 of the 16 known VDR activators


How does the incidence of multiple sclerosis vary with race?

Large Language Model conclusion to question:
The incidence of MS varies significantly by race and ethnicity, with whites of European ancestry historically being the most affected. However, recent studies have shown an increasing incidence among African Americans and unique disease characteristics and progression in African Americans and Hispanics:
full response by Perplexity Feb 2024