| Title: | Vitamin D genetic risk scores in multiple sclerosis |
| Journal: | Journal of Neurology |
| Published: | 5 Nov 2022 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/36334133/ |
| DOI: | https://doi.org/10.1007/s00415-022-11466-4 |
| URL: | https://link.springer.com/content/pdf/10.1007/s00415-022-11466-4.pdf |
Publication 10661
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Abstract
BackgroundLow serum 25(OH)D3 (vD) is an environmental risk factor for multiple sclerosis (MS). Lower vD levels during early disease may be associated with long-term disability. Determinants of serum vD levels in healthy individuals include supplementation behaviour and genetic factors. These determinants have been less well studied in people with MS (pwMS).MethodsWe developed a vD-weighted genetic risk score (GRS) and validated this in 373,357 UK Biobank participants without MS. We measured serum 25(OH)D3 and genotyped six vD-associated SNPs (rs12785878, rs10741657, rs17216707, rs10745742, rs8018720, rs2282679) in a cohort of pwMS (n = 315) with age and geographically matched controls (n = 232). We then assessed predictors of serum vD concentration in this cohort.ResultsThe GRS was strongly associated with vD status in the Biobank cohort (p < 2 × 10-16). vD supplementation, having MS, lower BMI, increased age and supplementation dose were associated with higher vD levels (false discovery rate, FDR < 5%). In multivariable models adjusting for supplementation, BMI, age, sex, and MS status, the GRS was strongly associated with vD level (p = 0.004), but not in those who supplemented (p = 0.47).ConclusionsOur findings suggest that vD supplementation is the major determinant of vD level in pwMS, with genetic determinants playing a far smaller role.</p>
5 Authors
- Ashvin Kuri
- Nicola Vickaryous
- Amine Awad
- Benjamin Meir Jacobs
- Ruth Dobson
1 Application
| Application ID | Title |
|---|---|
| 43101 | What is the vitamin D status of people with MS in the UK, how does this interact with risk factors associated with MS development, and what are the downstream consequences? |
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