Genome-wide gene-environment interaction study uncovers 162 vitamin D status variants using a precise ambient UVB measure
Year: 2025
Type: article
Study design: Observational Study
Abstract: Vitamin D status is influenced by genetic and environmental factors—primarily sun exposure. Using satellite weather data, we estimated an ambient UVB dose for each participant based on residential address and date of sampling. We conducted genome-wide tests in 338,977 UK Biobank White British participants, adjusted for age, sex, supplements, UVB dose, and 10 principal components to account for population structure. We applied three models to test for genetic effects: marginal only, main and interaction, and joint effects. We identified 307 variants associated with standardised log-transformed 25-hydroxyvitamin D (25OHD) concentration, 162 of which were not previously identified in GWAS. We identify an increase in SNP-heritability by increasing ambient UVB exposure quintiles (h 2 Q1 = 8.48% vs . h 2 Q5 = 15.56%). Downstream annotation implicated genes in the 25OHD pathway, including the circadian regulator, BMAL1 . This and further findings suggest that vitamin D status and circadian rhythm may be entangled and that vitamin D metabolites may have a role as mediators of seasonal physiological fluctuations, including metabolism, and in turn explain the established associations with lipid metabolism pathways.
Source: Nature Communications
Institutions: Ollscoil na Gaillimhe – University of Galway, Trinity College Dublin, University of Southern Denmark, Institute of Genetics and Cancer, MRC Human Genetics Unit, University of Edinburgh, National University of Ireland, Maynooth, Royal Netherlands Meteorological Institute, St. James's Hospital, Medical University of Graz, Heidelberg University, Synlab (Germany), Edinburgh Cancer Research
Language: English
Topic: Vitamin D Research Studies
Subfield: Pathology and Forensic Medicine
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $6,990
Awards: G1689944598, G1737722923, G2402982190, European Collaborative Project on Inflamation and Vascular Wall Remodelling in Atherosclerosis, G2755244757, G2835930995, G3001543491, FRAILMatics: Mathematical research and big data analytics towards the development of the next generation of transdisciplinary diagnostics for the assessment of physiological vulnerability in older adults: challenge-based disruptive technology initiative, G3345895242, G3763406989, Personalized diagnostics and treatment of high risk coronary artery disease patients., G4268089617, G434337789, G4801199537, G4937468798, G5597712516, G5783078658, G6260303519, SFI Centre for Research Training in Genomics Data Science, G8512683158, Doctorate School in Integrated Genomics Research, G970400076
OpenAlex ID: W4416795519