Skip to content

Genome-wide Association Study for Vitamin D Levels Reveals 69 Independent Loci

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)327-337
JournalAmerican Journal of Human Genetics
Issue number3
DateAccepted/In press - 22 Jan 2020
DatePublished (current) - 13 Feb 2020


We aimed to increase our understanding of the genetic determinants of vitamin D levels by undertaking a large-scale genome-wide as- sociation study (GWAS) of serum 25 hydroxyvitamin D (25OHD). To do so, we used imputed genotypes from 401,460 white British UK Biobank participants with available 25OHD levels, retaining single-nucleotide polymorphisms (SNPs) with minor allele frequency (MAF) > 0.1% and imputation quality score > 0.3. We performed a linear mixed model GWAS on standardized log-transformed 25OHD, adjusting for age, sex, season of measurement, and vitamin D supplementation. These results were combined with those from a previous GWAS including 42,274 Europeans. In silico functional follow-up of the GWAS results was undertaken to identify enrich- ment in gene sets, pathways, and expression in tissues, and to investigate the partitioned heritability of 25OHD and its shared herita- bility with other traits. Using this approach, the SNP heritability of 25OHD was estimated to 16.1%. 138 conditionally independent SNPs were detected (p value < 6.6 3 109) among which 53 had MAF < 5%. Single variant association signals mapped to 69 distinct loci, among which 63 were previously unreported. We identified enrichment in hepatic and lipid metabolism gene pathways and enriched expression of the 25OHD genes in liver, skin, and gastrointestinal tissues. We observed partially shared heritability between 25OHD and socio-economic traits, a feature which may be mediated through time spent outdoors. Therefore, through a large 25OHD GWAS, we identified 63 loci that underline the contribution of genes outside the vitamin D canonical metabolic pathway to the genetic architec- ture of 25OHD.



  • Full-text PDF (author’s accepted manuscript)

    Rights statement: This is the author accepted manuscript (AAM). The final published version (version of record) is available online via Elsevier at . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 806 KB, PDF document

    Embargo ends: 13/08/20

    Request copy

    Licence: CC BY-NC-ND


View research connections

Related faculties, schools or groups