30 distinct genes that influence vitamin D status found

Posted on: 02 December 2025

The study involved collaborators from Maynooth University, the Netherlands, UK, Denmark, Austria, and Germany and is published in the journal Nature Communications.

Sunshine, specifically UVB radiation, induces production of vitamin D in exposed skin, leading to a seasonal trend: vitamin D concentration usually peaks in the summer and is lowest at the end of the winter. Vitamin D deficiency, which can lead to other illness, is very common in Europe due to our indoor lifestyle and northerly location.

The authors analysed data from over 330,000 participants from the UK Biobank and included a more sophisticated measure of sunshine exposure than earlier research. Other studies often only consider whether vitamin D was measured in the summer or winter, which does not accurately account for the changing intensity of sunshine throughout the year and allows strong environmental influences to overshadow small genetic effects.

In this new study, the authors used satellite data to retrieve daily UVB measurements at each participant’s home address over the 5 months period up to the date of vitamin D measurement. This was used to calculate a precise ambient UVB dose for each person.

The approach proved to be highly successful. By quantifying the environmental influences and investigating the links between genes and sunshine (gene-environment interactions), the authors identified over 300 genetic variants to be linked with vitamin D status, pointing to its various functions in the body.

Firstly, several of the newly identified genes are linked with circadian rhythm, the body’s natural 24-hour cycle. This suggests, for the first time, a link between vitamin D status, circadian rhythm, and an innate seasonal rhythm. Although it is still unclear in humans, many animals are known to have seasonal rhythms, which are natural built-in cycles of metabolism or behaviour such as shedding fur or hibernation.

Secondly, many of the identified genes are important for steroid and lipid metabolism. This indicates that BMI and vitamin D status may be intertwined, with individuals who are vitamin D deficient being more likely to develop higher BMI and vice versa. BMI is also thought to change by season—higher in winter than summer.

Finally, several of the genes produce enzymes that are important for the excretion of a wide variety of molecules from the body, such as drugs, hormones, or vitamin D. Sometimes this process is reversible, which suggests that some forms of discarded vitamin D metabolites can be recycled back into its active form (25-hydroxyvitamin D). This could have important clinical implications: if there are metabolites beyond 25-hydroxyvitamin D that can be converted into the active form, we may need to reevaluate how we measure vitamin D deficiency.

The study paves the way for the development of a new generation of personalised vitamin D supplementation recommendations, which could be made possible in the future by integrating genomic information with detailed environmental measures, including sunshine availability where an individual resides.

Dr Rasha Shraim, postdoctoral researcher at the Department of Public Health and Primary Care, School of Medicine, Trinity College and first author, said:

“Our study highlights the complexity of the relationship between our genes and the surrounding environment. We can learn a lot about human health from studying them together. In this case, we find a link between vitamin D and circadian rhythm, and this also raises interesting new research questions.”

Professor Lina Zgaga, Professor in Epidemiology, Department of Public Health and Primary Care, School of Medicine, Trinity College and the principal investigator, said:

“Our genetic makeup is shaped by millions of years of interaction with the environment, so it is only logical that genetic studies should account for the environment but doing so is often challenging in practice. A surprisingly small number of gene-environment interactions have been described to date, so several gene-UVB interactions we uncovered are noteworthy and highlight how genetic and environmental factors are deeply intertwined.”

“We are in an era where understanding health means linking data across traditional boundaries. Working with Tropospheric Emissions Monitoring Internet Service enabled us to integrate genetic and environmental information at scale, revealing how complex interactions shape individual and population health. The abundance of new insights we gained shows how important it is to study genetic and environmental factors together rather than in isolation.”

Professor Ross McManus, Department of Clinical Medicine and Trinity Translational Medicine Institute who co-supervised the study noted:

“More broadly, this study shows the importance of accurately quantifying environmental factors in health and disease. Many common inherited conditions have an environmental risk component which is often unknown or poorly characterised. I think this really illustrates that we need to better understand such components to continue unmasking genetic drivers of these complex conditions.”

READ: You can read the full paper ‘Genome-wide gene-environment interaction study uncovers 162 vitamin D status variants using a precise ambient UVB measure’ in Nature Communications at the following link: https://www.nature.com/articles/s41467-025-65820-x

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