Genome-wide gene-environment interaction study uncovers 162 vitamin D status variants using a precise ambient UVB...

Area of Science:

• Genetics
• Nutritional Science
• Environmental Health

Background:

• Vitamin D status is influenced by a combination of genetic predispositions and environmental elements, with ultraviolet B (UVB) radiation from sunlight being a primary determinant.
• Understanding the interplay between genetic factors, environmental exposures like UVB, and vitamin D levels is crucial for public health and personalized medicine.

Purpose of the Study:

• To conduct a genome-wide association study (GWAS) to identify genetic variants associated with 25-hydroxyvitamin D (25OHD) concentration.
• To investigate the influence of ambient UVB exposure on SNP-heritability of 25OHD.
• To explore potential links between vitamin D metabolism, circadian rhythm, and seasonal physiological changes.

Main Methods:

• Utilized UK Biobank data from 338,977 White British participants.
• Estimated ambient UVB dose for each participant using satellite weather data based on residential address and sampling date.
• Performed genome-wide association tests, adjusting for covariates including age, sex, supplement use, UVB dose, and population structure principal components.
• Applied marginal, main and interaction, and joint effects models to analyze genetic associations.

Main Results:

• Identified 307 genetic variants associated with 25OHD concentration, with 162 novel discoveries.
• Demonstrated an increase in SNP-heritability of 25OHD with increasing ambient UVB exposure quintiles (from 8.48% to 15.56%).
• Downstream gene annotation implicated genes within the 25OHD pathway, notably the circadian regulator BMAL1.

Conclusions:

• Vitamin D status and circadian rhythm appear to be interconnected.
• Vitamin D metabolites may play a role in mediating seasonal physiological fluctuations, potentially explaining associations with lipid metabolism pathways.
• Genetic and environmental factors significantly contribute to variations in vitamin D levels, with implications for understanding broader physiological processes.