Association between 25(OH) vitamin D and multiple sclerosis: cohort, shared genetics, and Causality.

IF 4.4 2区医学 Q1 NUTRITION & DIETETICS

Nutrition Journal Pub Date : 2024-11-30 DOI:10.1186/s12937-024-01059-4

Xing-Hao Yu, Hui-Min Lu, Jun Li, Ming-Zhu Su, Xiao-Min Li, Yi Jin

{"title":"Association between 25(OH) vitamin D and multiple sclerosis: cohort, shared genetics, and Causality.","authors":"Xing-Hao Yu, Hui-Min Lu, Jun Li, Ming-Zhu Su, Xiao-Min Li, Yi Jin","doi":"10.1186/s12937-024-01059-4","DOIUrl":null,"url":null,"abstract":"Background: Multiple Sclerosis (MS), an autoimmune disorder causing demyelination and neurological damage, has been linked to 25-hydroxyvitamin D (25OHD) levels, suggesting its role in immune response and MS onset. This study used GWAS datasets to investigate genetic associations between 25OHD and MS.Methods: We utilized a large-scale prospective cohort to evaluate serum 25OHD levels and MS risk. Linkage Disequilibrium Score Regression (LDSC) assessed genetic correlations between 25OHD levels and MS. Cross-trait genome-wide pleiotropy analysis revealed shared genetic loci. MAGMA analysis identified pleiotropic genes, enriched tissues, and gene sets. Stratified LDSC estimated tissue-specific and cell-specific heritability enrichment, and multi-trait co-localization analysis identified shared immune cell subsets. Bidirectional Mendelian Randomization (MR) assessed the causal association between 25OHD and MS risk.Results: The observational study found a nonlinear relationship between 25OHD levels and MS risk, with the lowest quartile showing significant risk elevation. Our findings revealed shared genetic structure between 25OHD levels and MS, suggesting a common biological pathway involving immune function and CNS integrity. We found 24 independent loci shared between 25OHD levels and MS risk, enriched in brain tissues and involved in pathways like LDL, HDL, and TG metabolism. Four loci (6p24.3, 6p22.2, 12q14.1, and 19p13.2) had strong co-localization evidence, with mapped genes as potential drug targets. Bidirectional MR analysis supported a causal effect of 25OHD levels on MS risk, suggesting 25OHD supplementation could modulate MS risk.Conclusion: This study reveals the complex relationship between 25OHD levels and MS, indicating that higher levels are not always advantageous and recommending moderation in supplementation. We identified SMARCA4 as a potential therapeutic target and detailed key pathways influencing this interaction.","PeriodicalId":19203,"journal":{"name":"Nutrition Journal","volume":"23 1","pages":"151"},"PeriodicalIF":4.4000,"publicationDate":"2024-11-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11608472/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nutrition Journal","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12937-024-01059-4","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"NUTRITION & DIETETICS","Score":null,"Total":0}

引用次数: 0

Abstract

Background: Multiple Sclerosis (MS), an autoimmune disorder causing demyelination and neurological damage, has been linked to 25-hydroxyvitamin D (25OHD) levels, suggesting its role in immune response and MS onset. This study used GWAS datasets to investigate genetic associations between 25OHD and MS.

Methods: We utilized a large-scale prospective cohort to evaluate serum 25OHD levels and MS risk. Linkage Disequilibrium Score Regression (LDSC) assessed genetic correlations between 25OHD levels and MS. Cross-trait genome-wide pleiotropy analysis revealed shared genetic loci. MAGMA analysis identified pleiotropic genes, enriched tissues, and gene sets. Stratified LDSC estimated tissue-specific and cell-specific heritability enrichment, and multi-trait co-localization analysis identified shared immune cell subsets. Bidirectional Mendelian Randomization (MR) assessed the causal association between 25OHD and MS risk.

Results: The observational study found a nonlinear relationship between 25OHD levels and MS risk, with the lowest quartile showing significant risk elevation. Our findings revealed shared genetic structure between 25OHD levels and MS, suggesting a common biological pathway involving immune function and CNS integrity. We found 24 independent loci shared between 25OHD levels and MS risk, enriched in brain tissues and involved in pathways like LDL, HDL, and TG metabolism. Four loci (6p24.3, 6p22.2, 12q14.1, and 19p13.2) had strong co-localization evidence, with mapped genes as potential drug targets. Bidirectional MR analysis supported a causal effect of 25OHD levels on MS risk, suggesting 25OHD supplementation could modulate MS risk.

Conclusion: This study reveals the complex relationship between 25OHD levels and MS, indicating that higher levels are not always advantageous and recommending moderation in supplementation. We identified SMARCA4 as a potential therapeutic target and detailed key pathways influencing this interaction.

查看原文本刊更多论文

25（OH）维生素D与多发性硬化症之间的关系：队列、共享遗传和因果关系。

背景：多发性硬化症（MS）是一种引起脱髓鞘和神经损伤的自身免疫性疾病，与25-羟基维生素D （25OHD）水平有关，提示其在免疫反应和MS发病中的作用。本研究使用GWAS数据集调查25OHD和MS之间的遗传关联。方法：我们采用大规模前瞻性队列来评估血清25OHD水平和MS风险。连锁不平衡评分回归（LDSC）评估了25OHD水平与ms之间的遗传相关性，跨性状全基因组多效性分析显示了共享的遗传位点。MAGMA分析鉴定了多效性基因、富集的组织和基因集。分层LDSC估计了组织特异性和细胞特异性的遗传力富集，多性状共定位分析鉴定了共享的免疫细胞亚群。双向孟德尔随机化（MR）评估25OHD和MS风险之间的因果关系。结果：观察性研究发现25OHD水平与MS风险之间存在非线性关系，最低四分位数显示风险显著升高。我们的研究结果揭示了25OHD水平与MS之间共享的遗传结构，提示涉及免疫功能和中枢神经系统完整性的共同生物学途径。我们发现24个独立的基因座在25OHD水平和MS风险之间共享，这些基因座在脑组织中丰富，并参与LDL， HDL和TG代谢等途径。4个基因座（6p24.3、6p22.2、12q14.1和19p13.2）具有较强的共定位证据，定位的基因可能是潜在的药物靶点。双向磁共振分析支持25OHD水平对MS风险的因果效应，表明补充25OHD可以调节MS风险。结论：本研究揭示了25OHD水平与MS之间的复杂关系，提示较高的25OHD水平并不总是有利的，建议适度补充。我们确定了SMARCA4作为潜在的治疗靶点，并详细介绍了影响这种相互作用的关键途径。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Nutrition Journal NUTRITION & DIETETICS-

CiteScore

9.80

自引率

0.00%

发文量

审稿时长

4-8 weeks

期刊介绍： Nutrition Journal publishes surveillance, epidemiologic, and intervention research that sheds light on i) influences (e.g., familial, environmental) on eating patterns; ii) associations between eating patterns and health, and iii) strategies to improve eating patterns among populations. The journal also welcomes manuscripts reporting on the psychometric properties (e.g., validity, reliability) and feasibility of methods (e.g., for assessing dietary intake) for human nutrition research. In addition, study protocols for controlled trials and cohort studies, with an emphasis on methods for assessing dietary exposures and outcomes as well as intervention components, will be considered. Manuscripts that consider eating patterns holistically, as opposed to solely reductionist approaches that focus on specific dietary components in isolation, are encouraged. Also encouraged are papers that take a holistic or systems perspective in attempting to understand possible compensatory and differential effects of nutrition interventions. The journal does not consider animal studies. In addition to the influence of eating patterns for human health, we also invite research providing insights into the environmental sustainability of dietary practices. Again, a holistic perspective is encouraged, for example, through the consideration of how eating patterns might maximize both human and planetary health.