This webpage summarizes the analyses published in Revez et al. 2020 Nature Communications. It includes the following sections (click on tabs above - documented with code):
- Pheno: Section describing:
- How data were download and extracted for analyses
- Exploratory analyses performed
- How the phenotype files used in the GWAS section were created
- GWAS: Section describing how genome-wide association (GWA) analyses were performed and the results of those analyses.
- BMI: Section describing the analyses conducted to assess the relationship between vitamin D and body mass index (BMI).
- Meta-analysis: Section with meta-analysis of our GWAS results with those from the SUNLIGHT Consortium
- Heritability: Section where we estimate the proportion of phenotypic variability explained by genetic variants.
- Annotation: Section with follow-up analyses on GWA results.
- SMR: Section with summary Mendelian randomization (SMR) analyses, which integrate our GWAS results with results from expression (eQTL) and methylation (mQTL) quantitative trait loci GWAS results
- GSMR: Section with results from our generalized summary Mendelian randomization (GSMR) analyses, which test for putative causal association between vitamin D and other traits
- Stratified GWAS: Section with GWAS on vitamin D levels measured in (1) Summer, and (2) Winter
- vQTL: Section with variance QTL (vQTL) GWA analysis on unrelated individuals with European ancestry
Study summary:
Vitamin D deficiency is a candidate risk factor for a range of adverse health outcomes, including psychiatric traits. We conducted a genome-wide association study of 25 hydroxyvitamin D (25OHD) concentration (the main metabolite used to assess vitamin D status) in 417,580 Europeans. We identified 143 independent loci implicating genes involved in lipid and lipoprotein metabolism, dermal tissue properties, and the sulphonation and glucuronidation of 25OHD. Using Mendelian randomization models, we found no robust evidence that 25OHD concentration has causal effects on candidate phenotypes (e.g. schizophrenia), but many phenotypes have (direct or indirect) causal effects on 25OHD concentration, clarifying the epidemiological relationship between 25OHD status and the health outcomes examined in this study.
GWAS summary statistics are available in https://cnsgenomics.com/content/data.