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Vitamin D genetic risk scores in multiple sclerosis

BACKGROUND: Low serum 25(OH)D(3) (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 det...

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Autores principales: Kuri, Ashvin, Vickaryous, Nicola, Awad, Amine, Jacobs, Benjamin Meir, Dobson, Ruth
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Springer Berlin Heidelberg 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886624/
https://www.ncbi.nlm.nih.gov/pubmed/36334133
http://dx.doi.org/10.1007/s00415-022-11466-4
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author Kuri, Ashvin
Vickaryous, Nicola
Awad, Amine
Jacobs, Benjamin Meir
Dobson, Ruth
author_facet Kuri, Ashvin
Vickaryous, Nicola
Awad, Amine
Jacobs, Benjamin Meir
Dobson, Ruth
author_sort Kuri, Ashvin
collection PubMed
description BACKGROUND: Low serum 25(OH)D(3) (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). METHODS: We developed a vD-weighted genetic risk score (GRS) and validated this in 373,357 UK Biobank participants without MS. We measured serum 25(OH)D(3) 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. RESULTS: The 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). CONCLUSIONS: Our findings suggest that vD supplementation is the major determinant of vD level in pwMS, with genetic determinants playing a far smaller role.
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spelling pubmed-98866242023-02-01 Vitamin D genetic risk scores in multiple sclerosis Kuri, Ashvin Vickaryous, Nicola Awad, Amine Jacobs, Benjamin Meir Dobson, Ruth J Neurol Original Communication BACKGROUND: Low serum 25(OH)D(3) (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). METHODS: We developed a vD-weighted genetic risk score (GRS) and validated this in 373,357 UK Biobank participants without MS. We measured serum 25(OH)D(3) 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. RESULTS: The 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). CONCLUSIONS: Our findings suggest that vD supplementation is the major determinant of vD level in pwMS, with genetic determinants playing a far smaller role. Springer Berlin Heidelberg 2022-11-05 2023 /pmc/articles/PMC9886624/ /pubmed/36334133 http://dx.doi.org/10.1007/s00415-022-11466-4 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Original Communication
Kuri, Ashvin
Vickaryous, Nicola
Awad, Amine
Jacobs, Benjamin Meir
Dobson, Ruth
Vitamin D genetic risk scores in multiple sclerosis
title Vitamin D genetic risk scores in multiple sclerosis
title_full Vitamin D genetic risk scores in multiple sclerosis
title_fullStr Vitamin D genetic risk scores in multiple sclerosis
title_full_unstemmed Vitamin D genetic risk scores in multiple sclerosis
title_short Vitamin D genetic risk scores in multiple sclerosis
title_sort vitamin d genetic risk scores in multiple sclerosis
topic Original Communication
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9886624/
https://www.ncbi.nlm.nih.gov/pubmed/36334133
http://dx.doi.org/10.1007/s00415-022-11466-4
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