Vitamin D-associated genetic variants in the Brazilian population: Investigating potential instruments for Mendelian randomization

• Published in: Biomédica
• Main Authors: Caroline de Souza Silverio, Carolina Bonilla
• Format: Article in Journal/Newspaper
• Language: English; Spanish
• Published: Instituto Nacional de Salud 2024
• Subjects: vitamin d; genome-wide association study; polymorphisms; single nucleotide; vitamin d-binding protein; vitamin d3 24-hydroxylase; 5-hydroxyvitamin d3 1-alphahydroxylase; leishmania braziliensis; Medicine; R; Arctic medicine. Tropical medicine; RC955-962; Arctic
• Online Access: https://doi.org/10.7705/biomedica.6972; https://doaj.org/article/40f6300594ad44d88df806b3f6187ed1

Introduction. Vitamin D is required for bone and mineral metabolism and participates in the regulation of the immune response. It is also linked to several chronic diseases and conditions, usually in populations of European descent. Brazil presents a high prevalence of vitamin D deficiency and insufficiency despite the widespread availability of sunlight in the country. Thus, it is important to investigate the role of vitamin D as a risk factor for disease and to establish causal relationships between vitamin D levels and health-related outcomes in the Brazilian population. Objective. To examine genetic variants identified as determinants of serum vitamin D in genome-wide association studies of European populations and check whether the same associations are present in Brazil. If so, these single nucleotide polymorphisms (SNPs) could be developed locally as proxies to use in genetically informed causal inference methods, such as Mendelian randomization. Materials and methods. We extracted SNPs associated with vitamin D from the genomewide association studies catalog. We did a literature search to select papers ascertaining these variants and vitamin D concentrations in Brazil. Results. GC was the gene with the strongest association with vitamin D levels, in agreement with existing findings in European populations. However, VDR was the most investigated gene, regardless of its non-existing association with vitamin D in the genomewide association studies. Conclusions. More research is needed to validate sound proxies for vitamin D levels in Brazil, for example, prioritizing GC rather than VDR.