Genetic and molecular factors affecting vitamin B12 levels in Estonian Biobank

Abstract

Vitamin B12 is an essential micronutrient involved in DNA synthesis, red blood cell formation, and neurological function. Low levels of vitamin B12 are associated with a variety of clinical conditions, including pernicious anemia, serious neurological problems, and cardiometabolic diseases. In this study, we analyzed circulating vitamin B12 levels in 74,669 participants from the Estonian Biobank using a genome-wide association study. Associated single-nucleotide variants were annotated to identify genes and molecular mechanisms related to vitamin B12 transport and metabolism, with additional focus on coding variants of potential biological relevance. From this analysis, we identified 26 genome-wide significant loci comprising 8,876 candidate variants that mapped to the vicinity of 527 genes, with the strongest signals in genes involved in vitamin B12 transport, absorption and metabolism. These findings expand our understanding of genetic factors affecting circulating vitamin B12 levels, and provide a structural basis for understanding how specific genetic coding variants may affect the transport molecular mechanisms of vitamin B12 transport.