Genetic correlates of vitamin D-binding protein and 25-hydroxyvitamin D in neonatal dried blood spots
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The vitamin D binding protein (DBP), encoded by the group-specific component (GC) gene, is a component of the vitamin D system. In a genome-wide association study of DBP concentration in 65,589 neonates we identify 26 independent loci, 17 of which are in or close to the GC gene, with fine-mapping identifying 2 missense variants on chromosomes 12 and 17 (within SH2B3 and GSDMA, respectively). When adjusted for GC haplotypes, we find 15 independent loci distributed over 10 chromosomes. Mendelian randomization analyses identify a unidirectional effect of higher DBP concentration and (a) higher 25-hydroxyvitamin D concentration, and (b) a reduced risk of multiple sclerosis and rheumatoid arthritis. A phenome-wide association study confirms that higher DBP concentration is associated with a reduced risk of vitamin D deficiency. Our findings provide valuable insights into the influence of DBP on vitamin D status and a range of health outcomes.
| Originalsprog | Engelsk |
|---|---|
| Artikelnummer | 852 |
| Tidsskrift | Nature Communications |
| Vol/bind | 14 |
| Antal sider | 16 |
| ISSN | 2041-1723 |
| DOI | |
| Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 02/01/22. The authors thank GenomeDK and Aarhus University for providing computational resources and support that contributed to these research results. This research has been conducted using the UK Biobank Resource under Application Number 12505. This study was supported by the Danish National Research Foundation, via a Niels Bohr Professorship to John McGrath. Oleguer Plana-Ripoll is supported by a Lundbeck Foundation Fellowship (R345-2020-1588) and has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 837180. Bjarni Vilhjalmsson was also supported by a Lundbeck Foundation Fellowship (R335-2019-2339). Liselotte V Petersen was supported by a Lundbeck Foundation grant (R276-2018-4581) and by the NIMH (R01MH120170). The iPSYCH team was supported by grants from the Lundbeck Foundation (R102-A9118, R155-2014-1724, and R248-2017-2003) and the Universities and University Hospitals of Aarhus and Copenhagen. The Anorexia Nervosa Genetics Initiative (ANGI) was an initiative of the Klarman Family Foundation. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). Naomi Wray is supported by the National Health and Research Council (1113400, 1173790). Anorexia nervosa GWAS data: Klarman Family Foundation. CMB is supported by NIMH (R01MH120170; R01 MH124871; R01MH119084; R01MH118278; R01 MH124871); Brain and Behavior Research Foundation Distinguished Investigator Grant; Swedish Research Council (Vetenskapsrådet, award: 538-2013-8864); Lundbeck Foundation (Grant no. R276-2018-4581).
Funding Information:
C.M.B. reports Shire (grant recipient, Scientific Advisory Board member); Lundbeckfonden (grant recipient); Pearson (author, royalty recipient); Equip Health Inc. (Clinical Advisory Board). The remaining authors declare no competing interests.
Funding Information:
The Genotype-Tissue Expression (GTEx) Project was supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The data used for the analyses described in this manuscript were obtained from the GTEx Portal on 02/01/22. The authors thank GenomeDK and Aarhus University for providing computational resources and support that contributed to these research results. This research has been conducted using the UK Biobank Resource under Application Number 12505. This study was supported by the Danish National Research Foundation, via a Niels Bohr Professorship to John McGrath. Oleguer Plana-Ripoll is supported by a Lundbeck Foundation Fellowship (R345-2020-1588) and has received funding from the European Union’s Horizon 2020 research and innovation program under the Marie Sklodowska-Curie grant agreement No 837180. Bjarni Vilhjalmsson was also supported by a Lundbeck Foundation Fellowship (R335-2019-2339). Liselotte V Petersen was supported by a Lundbeck Foundation grant (R276-2018-4581) and by the NIMH (R01MH120170). The iPSYCH team was supported by grants from the Lundbeck Foundation (R102-A9118, R155-2014-1724, and R248-2017-2003) and the Universities and University Hospitals of Aarhus and Copenhagen. The Anorexia Nervosa Genetics Initiative (ANGI) was an initiative of the Klarman Family Foundation. The Danish National Biobank resource was supported by the Novo Nordisk Foundation. High-performance computer capacity for handling and statistical analysis of iPSYCH data on the GenomeDK HPC facility was provided by the Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing, iSEQ, Aarhus University, Denmark (grant to ADB). Naomi Wray is supported by the National Health and Research Council (1113400, 1173790). Anorexia nervosa GWAS data: Klarman Family Foundation. CMB is supported by NIMH (R01MH120170; R01 MH124871; R01MH119084; R01MH118278; R01 MH124871); Brain and Behavior Research Foundation Distinguished Investigator Grant; Swedish Research Council (Vetenskapsrådet, award: 538-2013-8864); Lundbeck Foundation (Grant no. R276-2018-4581).
Publisher Copyright:
© 2023, The Author(s).
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