{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T01:45:53Z","timestamp":1784166353030,"version":"3.55.0"},"reference-count":104,"publisher":"MDPI AG","issue":"20","license":[{"start":{"date-parts":[[2022,10,20]],"date-time":"2022-10-20T00:00:00Z","timestamp":1666224000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Health and Medical Research Council (Australia)","award":["GNT1123603"],"award-info":[{"award-number":["GNT1123603"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Twin studies suggest a considerable genetic contribution to the variability in 25-hydroxyvitamin D (25(OH)D) concentrations, reporting heritability estimates up to 80% in some studies. While genome-wide association studies (GWAS) suggest notably lower rates (13\u201316%), they have identified many independent variants that associate with serum 25(OH)D concentrations. These discoveries have provided some novel insight into the metabolic pathway, and in this review we outline findings from GWAS studies to date with a particular focus on 35 variants which have provided replicating evidence for an association with 25(OH)D across independent large-scale analyses. Some of the 25(OH)D associating variants are linked directly to the vitamin D metabolic pathway, while others may reflect differences in storage capacity, lipid metabolism, and pathways reflecting skin properties. By constructing a genetic score including these 25(OH)D associated variants we show that genetic differences in 25(OH)D concentrations persist across the seasons, and the odds of having low concentrations (&lt;50 nmol\/L) are about halved for individuals in the highest 20% of vitamin D genetic score compared to the lowest quintile, an impact which may have notable influences on retaining adequate levels. We also discuss recent studies on personalized approaches to vitamin D supplementation and show how Mendelian randomization studies can help inform public health strategies to reduce adverse health impacts of vitamin D deficiency.<\/jats:p>","DOI":"10.3390\/nu14204408","type":"journal-article","created":{"date-parts":[[2022,10,21]],"date-time":"2022-10-21T00:34:30Z","timestamp":1666312470000},"page":"4408","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Genetic Determinants of 25-Hydroxyvitamin D Concentrations and Their Relevance to Public Health"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3670-9399","authenticated-orcid":false,"given":"Elina","family":"Hypp\u00f6nen","sequence":"first","affiliation":[{"name":"Australian Centre for Precision Health, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"},{"name":"South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8485-8930","authenticated-orcid":false,"given":"Karani S.","family":"Vimaleswaran","sequence":"additional","affiliation":[{"name":"Hugh Sinclair Unit of Human Nutrition, Department of Food and Nutritional Sciences, University of Reading, Reading RG6 6DZ, UK"},{"name":"The Institute for Food, Nutrition and Health (IFNH), University of Reading, Reading RG6 6DZ, UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Australian Centre for Precision Health, Clinical and Health Sciences, University of South Australia, Adelaide, SA 5001, Australia"},{"name":"South Australian Health and Medical Research Institute, Adelaide, SA 5001, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,10,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"371","DOI":"10.1359\/jbmr.2001.16.2.371","article-title":"Genetic Contribution to Bone Metabolism, Calcium Excretion, and Vitamin D and Parathyroid Hormone Regulation","volume":"16","author":"Hunter","year":"2001","journal-title":"J. Bone Miner. Res. Off. J. Am. Soc. Bone Miner. Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1093\/ajcn\/88.2.441","article-title":"Evidence for Genetic Regulation of Vitamin D Status in Twins with Multiple Sclerosis","volume":"88","author":"Orton","year":"2008","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/sj.ejcn.1602959","article-title":"Genetic and Non-Genetic Correlates of Vitamins K and D","volume":"63","author":"Shea","year":"2009","journal-title":"Eur. J. Clin. Nutr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.jsbmb.2006.12.053","article-title":"A Genome-Wide Linkage Scan for 25-OH-D(3) and 1,25-(OH)2-D3 Serum Levels in Asthma Families","volume":"103","author":"Wjst","year":"2007","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1097\/MNH.0b013e328346d6ba","article-title":"Determinants of Vitamin D Status: Focus on Genetic Variations","volume":"20","author":"Berry","year":"2011","journal-title":"Curr. Opin. Nephrol. Hypertens."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/j.ijpp.2018.01.005","article-title":"The Roles of Vitamin D and Cutaneous Vitamin D Production in Human Evolution and Health","volume":"23","author":"Jablonski","year":"2018","journal-title":"Int. J. Paleopathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","article-title":"The NHGRI-EBI GWAS Catalog of Published Genome-Wide Association Studies, Targeted Arrays and Summary Statistics 2019","volume":"47","author":"Buniello","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2739","DOI":"10.1093\/hmg\/ddq155","article-title":"Genome-Wide Association Study of Circulating Vitamin D Levels","volume":"19","author":"Ahn","year":"2010","journal-title":"Hum. Mol. Genet."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.jsbmb.2010.06.013","article-title":"Genome-Wide Association Study of Vitamin D Concentrations in Hispanic Americans: The IRAS Family Study","volume":"122","author":"Engelman","year":"2010","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/S0140-6736(10)60588-0","article-title":"Common Genetic Determinants of Vitamin D Insufficiency: A Genome-Wide Association Study","volume":"376","author":"Wang","year":"2010","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1495","DOI":"10.1007\/s00439-012-1185-z","article-title":"Genome-Wide Association Analysis of Circulating Vitamin D Levels in Children with Asthma","volume":"131","author":"Lange","year":"2012","journal-title":"Hum. Genet."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"578","DOI":"10.1038\/gene.2014.52","article-title":"Genome-Wide Association Study of Vitamin D Levels in Children: Replication in the Western Australian Pregnancy Cohort (Raine) Study","volume":"15","author":"Anderson","year":"2014","journal-title":"Genes Immun."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1016\/j.jsbmb.2015.12.014","article-title":"Genome-Wide Association Study of 25(OH) Vitamin D Concentrations in Punjabi Sikhs: Results of the Asian Indian Diabetic Heart Study","volume":"158","author":"Sapkota","year":"2016","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1016\/j.ajhg.2017.06.014","article-title":"Low-Frequency Synonymous Coding Variation in CYP2R1 Has Large Effects on Vitamin D Levels and Risk of Multiple Sclerosis","volume":"101","author":"Manousaki","year":"2017","journal-title":"Am. J. Hum. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1380","DOI":"10.1210\/jc.2017-01802","article-title":"Transethnic Evaluation Identifies Low-Frequency Loci Associated with 25-Hydroxyvitamin D Concentrations","volume":"103","author":"Hong","year":"2018","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"260","DOI":"10.1038\/s41467-017-02662-2","article-title":"Genome-Wide Association Study in 79,366 European-Ancestry Individuals Informs the Genetic Architecture of 25-Hydroxyvitamin D Levels","volume":"9","author":"Jiang","year":"2018","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"67","DOI":"10.3389\/fgene.2018.00067","article-title":"Genome-Wide Association Study of Serum 25-Hydroxyvitamin D in US Women","volume":"9","author":"Shi","year":"2018","journal-title":"Front. Genet."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Kampe, A., Enlund-Cerullo, M., Valkama, S., Holmlund-Suila, E., Rosendahl, J., Hauta-Alus, H., Pekkinen, M., Andersson, S., and Makitie, O. (2019). Genetic Variation in GC and CYP2R1 Affects 25-Hydroxyvitamin D Concentration and Skeletal Parameters: A Genome-Wide Association Study in 24-Month-Old Finnish Children. PLoS Genet., 15.","DOI":"10.1371\/journal.pgen.1008530"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1016\/j.ajhg.2020.01.017","article-title":"Genome-Wide Association Study for Vitamin D Levels Reveals 69 Independent Loci","volume":"106","author":"Manousaki","year":"2020","journal-title":"Am. J. Hum. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1038\/s41467-020-15421-7","article-title":"Genome-Wide Association Study Identifies 143 Loci Associated with 25 Hydroxyvitamin D Concentration","volume":"11","author":"Revez","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1534\/genetics.119.302792","article-title":"Genetic Contributions to Maternal and Neonatal Vitamin D Levels","volume":"214","author":"Traglia","year":"2020","journal-title":"Genetics"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Zheng, J.-S., Luan, J., Sofianopoulou, E., Sharp, S.J., Day, F.R., Imamura, F., Gundersen, T.E., Lotta, L.A., Sluijs, I., and Stewart, I.D. (2020). The Association between Circulating 25-Hydroxyvitamin D Metabolites and Type 2 Diabetes in European Populations: A Meta-Analysis and Mendelian Randomisation Analysis. PLoS Med., 17.","DOI":"10.1371\/journal.pmed.1003394"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1189","DOI":"10.3803\/EnM.2021.1241","article-title":"Unveiling Genetic Variants Underlying Vitamin D Deficiency in Multiple Korean Cohorts by a Genome-Wide Association Study","volume":"36","author":"Kim","year":"2021","journal-title":"Endocrinol. Metab."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"246","DOI":"10.1038\/s41467-020-20368-w","article-title":"A Comprehensive Re-Assessment of the Association between Vitamin D and Cancer Susceptibility Using Mendelian Randomization","volume":"12","author":"Ong","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Palmer, N.D., Lu, L., Register, T.C., Lenchik, L., Carr, J.J., Hicks, P.J., Smith, S.C., Xu, J., Dimitrov, L., and Keaton, J. (2021). Genome-Wide Association Study of Vitamin D Concentrations and Bone Mineral Density in the African American-Diabetes Heart Study. PLoS ONE, 16.","DOI":"10.1371\/journal.pone.0251423"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1093\/jn\/nxaa391","article-title":"Genetic Risk Score for Serum 25-Hydroxyvitamin D Concentration Helps to Guide Personalized Vitamin D Supplementation in Healthy Finnish Adults","volume":"151","author":"Sallinen","year":"2021","journal-title":"J. Nutr."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"721488","DOI":"10.3389\/fgene.2021.721488","article-title":"Genetic Link Determining the Maternal-Fetal Circulation of Vitamin D","volume":"12","author":"Sampathkumar","year":"2021","journal-title":"Front. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1002\/jbmr.4330","article-title":"Type 2 Diabetes Is Causally Associated With Reduced Serum Osteocalcin: A Genomewide Association and Mendelian Randomization Study","volume":"36","author":"Zeng","year":"2021","journal-title":"J. Bone Miner. Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1038\/s41586-021-04103-z","article-title":"Exome Sequencing and Analysis of 454,787 UK Biobank Participants","volume":"599","author":"Backman","year":"2021","journal-title":"Nature"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1260","DOI":"10.1038\/s41588-021-00892-1","article-title":"Whole-Exome Imputation within UK Biobank Powers Rare Coding Variant Association and Fine-Mapping Analyses","volume":"53","author":"Barton","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Benjamin, E.J., Dupuis, J., Larson, M.G., Lunetta, K.L., Booth, S.L., Govindaraju, D.R., Kathiresan, S., Keaney, J.F., Keyes, M.J., and Lin, J.-P. (2007). Genome-Wide Association with Select Biomarker Traits in the Framingham Heart Study. BMC Med. Genet., 8.","DOI":"10.1186\/1471-2350-8-S1-S11"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/s41586-019-1457-z","article-title":"Exome Sequencing of Finnish Isolates Enhances Rare-Variant Association Power","volume":"572","author":"Locke","year":"2019","journal-title":"Nature"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1038\/s41588-021-00870-7","article-title":"Computationally Efficient Whole-Genome Regression for Quantitative and Binary Traits","volume":"53","author":"Mbatchou","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1038\/s41588-020-00757-z","article-title":"Genetics of 35 Blood and Urine Biomarkers in the UK Biobank","volume":"53","author":"Tanigawa","year":"2021","journal-title":"Nat. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/s10038-021-00968-0","article-title":"Analyses of Biomarker Traits in Diverse UK Biobank Participants Identify Associations Missed by European-Centric Analysis Strategies","volume":"67","author":"Sun","year":"2022","journal-title":"J. Hum. Genet."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"ATVBAHA121316650","DOI":"10.1161\/ATVBAHA.121.316650","article-title":"Harnessing Whole Genome Polygenic Risk Scores to Stratify Individuals Based on Cardiometabolic Risk Factors and Biomarkers at Age 10 in the Lifecourse","volume":"42","author":"Richardson","year":"2022","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"365","DOI":"10.1152\/physrev.00014.2015","article-title":"Vitamin D: Metabolism, Molecular Mechanism of Action, and Pleiotropic Effects","volume":"96","author":"Christakos","year":"2016","journal-title":"Physiol. Rev."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"849","DOI":"10.1016\/j.steroids.2006.04.009","article-title":"Characterization of Rat and Human CYP2J Enzymes as Vitamin D 25-Hydroxylases","volume":"71","author":"Aiba","year":"2006","journal-title":"Steroids"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1731","DOI":"10.1093\/eurheartj\/ehab809","article-title":"Non-Linear Mendelian Randomization Analyses Support a Role for Vitamin D Deficiency in Cardiovascular Disease Risk","volume":"43","author":"Zhou","year":"2022","journal-title":"Eur. Heart J."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/(SICI)1098-1004(1999)14:1<45::AID-HUMU6>3.0.CO;2-J","article-title":"Identification of a Common PEX1 Mutation in Zellweger Syndrome","volume":"14","author":"Collins","year":"1999","journal-title":"Hum. Mutat."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/j.ymgme.2015.11.009","article-title":"Low Bone Mineral Density Is a Common Feature of Zellweger Spectrum Disorders","volume":"117","author":"Rush","year":"2016","journal-title":"Mol. Genet. Metab."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1042\/bj20020870","article-title":"CDNA Cloning, Gene Organization and Expression Analysis of Human Peptidylarginine Deiminase Type I","volume":"370","author":"Guerrin","year":"2003","journal-title":"Biochem. J."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1984","DOI":"10.1007\/s00018-005-5196-y","article-title":"The Peptidylarginine Deiminases Expressed in Human Epidermis Differ in Their Substrate Specificities and Subcellular Locations","volume":"62","author":"Enji","year":"2005","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"35959","DOI":"10.1074\/jbc.M302804200","article-title":"FoxO6, a Novel Member of the FoxO Class of Transcription Factors with Distinct Shuttling Dynamics *","volume":"278","author":"Jacobs","year":"2003","journal-title":"J. Biol. Chem."},{"key":"ref_45","first-page":"340","article-title":"Central FoxO3a and FoxO6 Expression Is Down-Regulated in Obesity Induced Diabetes but Not in Aging","volume":"120","author":"Zemva","year":"2012","journal-title":"Exp. Clin. Endocrinol. Diabetes Off. J. Ger. Soc. Endocrinol. Ger. Diabetes Assoc."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1093\/dnares\/7.3.233","article-title":"The Human Homologue of Flamingo, EGFL2, Encodes a Brain-Expressed Large Cadherin-like Protein with Epidermal Growth Factor-like Domains, and Maps to Chromosome 1p13.3-P21.1","volume":"7","author":"Vincent","year":"2000","journal-title":"DNA Res."},{"key":"ref_47","unstructured":"(2022, May 27). Ichthyosis Vulgaris Disease: Malacards\u2014Research Articles, Drugs, Genes, Clinical Trials. Available online: https:\/\/www.malacards.org\/card\/ichthyosis_vulgaris."},{"key":"ref_48","unstructured":"(2022, May 27). Peeling Skin Syndrome 6 Disease: Malacards\u2014Research Articles, Drugs, Genes, Clinical Trials. Available online: https:\/\/www.malacards.org\/card\/peeling_skin_syndrome_6."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1084\/jem.20040518","article-title":"RANKL-Induced DC-STAMP Is Essential for Osteoclastogenesis","volume":"200","author":"Kukita","year":"2004","journal-title":"J. Exp. Med."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1155","DOI":"10.1093\/hmg\/ddu510","article-title":"A Novel Common Variant in DCST2 Is Associated with Length in Early Life and Height in Adulthood","volume":"24","author":"Kooijman","year":"2015","journal-title":"Hum. Mol. Genet."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4143","DOI":"10.1021\/pr8002936","article-title":"Population Studies of Vitamin D Binding Protein Microheterogeneity by Mass Spectrometry Lead to Characterization of Its Genotype-Dependent O-Glycosylation Patterns","volume":"7","author":"Borges","year":"2008","journal-title":"J. Proteome Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1110","DOI":"10.1016\/j.celrep.2015.04.023","article-title":"Principles of Long Noncoding RNA Evolution Derived from Direct Comparison of Transcriptomes in 17 Species","volume":"11","author":"Hezroni","year":"2015","journal-title":"Cell Rep."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"254","DOI":"10.3934\/Neuroscience.2021014","article-title":"Identification of Potential and Novel Target Genes in Pituitary Prolactinoma by Bioinformatics Analysis","volume":"8","author":"Ghatnatti","year":"2021","journal-title":"AIMS Neurosci."},{"key":"ref_54","unstructured":"(2022, May 26). PubChem CPS1\u2014Carbamoyl-Phosphate Synthase 1 (Human), Available online: https:\/\/pubchem.ncbi.nlm.nih.gov\/gene\/CPS1\/human."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1152\/physrev.00058.2017","article-title":"The UDP-Glycosyltransferase (UGT) Superfamily: New Members, New Functions, and Novel Paradigms","volume":"99","author":"Meech","year":"2019","journal-title":"Physiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2052","DOI":"10.1210\/en.2013-2013","article-title":"Human UGT1A4 and UGT1A3 Conjugate 25-Hydroxyvitamin D3: Metabolite Structure, Kinetics, Inducibility, and Interindividual Variability","volume":"155","author":"Wang","year":"2014","journal-title":"Endocrinology"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1016\/j.ygeno.2005.08.017","article-title":"Bioinformatic Characterization of the SynCAM Family of Immunoglobulin-like Domain-Containing Adhesion Molecules","volume":"87","author":"Biederer","year":"2006","journal-title":"Genomics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.molmet.2017.11.010","article-title":"Cadm2 Regulates Body Weight and Energy Homeostasis in Mice","volume":"8","author":"Yan","year":"2018","journal-title":"Mol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"445","DOI":"10.1002\/cbf.2835","article-title":"New Perspectives on the Vitamin D Binding Protein","volume":"30","author":"Chun","year":"2012","journal-title":"Cell Biochem. Funct."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"5290","DOI":"10.1091\/mbc.e08-10-1071","article-title":"Distinct Roles for CARMIL Isoforms in Cell Migration","volume":"20","author":"Liang","year":"2009","journal-title":"Mol. Biol. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1006\/geno.1997.4945","article-title":"Cloning, Structural Organization Analysis, and Chromosomal Assignment of the Human Gene for the Neurosecretory Protein VGF","volume":"45","author":"Canu","year":"1997","journal-title":"Genomics"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"105855","DOI":"10.1016\/j.phrs.2021.105855","article-title":"The Molecular Mechanism of Vgf in Appetite, Lipids, and Insulin Regulation","volume":"172","author":"Benchoula","year":"2021","journal-title":"Pharmacol. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"6929","DOI":"10.1523\/JNEUROSCI.22-16-06929.2002","article-title":"VGF Is Required for Obesity Induced by Diet, Gold Thioglucose Treatment, and Agouti and Is Differentially Regulated in Pro-Opiomelanocortin- and Neuropeptide Y-Containing Arcuate Neurons in Response to Fasting","volume":"22","author":"Hahm","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.yexcr.2019.03.009","article-title":"High LINC00536 Expression Promotes Tumor Progression and Poor Prognosis in Bladder Cancer","volume":"378","author":"Li","year":"2019","journal-title":"Exp. Cell Res."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1081","DOI":"10.1016\/j.neuron.2019.09.027","article-title":"Trans-Synaptic Signaling through the Glutamate Receptor Delta-1 Mediates Inhibitory Synapse Formation in Cortical Pyramidal Neurons","volume":"104","author":"Fossati","year":"2019","journal-title":"Neuron"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"7711","DOI":"10.1073\/pnas.0402490101","article-title":"Genetic Evidence That the Human CYP2R1 Enzyme Is a Key Vitamin D 25-Hydroxylase","volume":"101","author":"Cheng","year":"2004","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1007\/s00439-018-1910-3","article-title":"The Coexistence of Copy Number Variations (CNVs) and Single Nucleotide Polymorphisms (SNPs) at a Locus Can Result in Distorted Calculations of the Significance in Associating SNPs to Disease","volume":"137","author":"Liu","year":"2018","journal-title":"Hum. Genet."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1127","DOI":"10.31616\/asj.2018.12.6.1127","article-title":"The Role of Vitamin D in the Pathogenesis of Adolescent Idiopathic Scoliosis","volume":"12","author":"Ng","year":"2018","journal-title":"Asian Spine J."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"24","DOI":"10.2174\/156652413804486214","article-title":"Functions of S100 Proteins","volume":"13","author":"Donato","year":"2013","journal-title":"Curr. Mol. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"38870","DOI":"10.1074\/jbc.M106219200","article-title":"Cloning of DGAT2, a Second Mammalian Diacylglycerol Acyltransferase, and Related Family Members","volume":"276","author":"Cases","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1038\/75651","article-title":"Obesity Resistance and Multiple Mechanisms of Triglyceride Synthesis in Mice Lacking Dgat","volume":"25","author":"Smith","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1016\/j.jdermsci.2007.12.009","article-title":"Histidase Expression in Human Epidermal Keratinocytes: Regulation by Differentiation Status and All-Trans Retinoic Acid","volume":"50","author":"Eckhart","year":"2008","journal-title":"J. Dermatol. Sci."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1006\/geno.1995.1219","article-title":"Molecular Cloning and Structural Characterization of the Human Histidase Gene (HAL)","volume":"29","author":"Suchi","year":"1995","journal-title":"Genomics"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1950","DOI":"10.1093\/carcin\/bgn160","article-title":"A Role for Ultraviolet Radiation Immunosuppression in Non-Melanoma Skin Cancer as Evidenced by Gene-Environment Interactions","volume":"29","author":"Welsh","year":"2008","journal-title":"Carcinogenesis"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1111\/phpp.12249","article-title":"The Effect of Epidermal Levels of Urocanic Acid on 25-Hydroxyvitamin D Synthesis and Inflammatory Mediators upon Narrowband UVB Irradiation","volume":"32","author":"Landeck","year":"2016","journal-title":"Photodermatol. Photoimmunol. Photomed."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1002\/jez.b.21139","article-title":"The search for non-chordate retinoic acid signaling: Lessons from chordates","volume":"310B","author":"Azambuja","year":"2008","journal-title":"J. Exp. Zoolog. B Mol. Dev. Evol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1376","DOI":"10.1074\/jbc.M408651200","article-title":"PDILT, a Divergent Testis-Specific Protein Disulfide Isomerase with a Non-Classical SXXC Motif That Engages in Disulfide-Dependent Interactions in the Endoplasmic Reticulum","volume":"280","author":"Hartigan","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"2417","DOI":"10.1002\/1873-3468.12767","article-title":"Sulfation of Vitamin D3 -Related Compounds-Identification and Characterization of the Responsible Human Cytosolic Sulfotransferases","volume":"591","author":"Kurogi","year":"2017","journal-title":"FEBS Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1124\/dmd.117.078428","article-title":"Polymorphic Human Sulfotransferase 2A1 Mediates the Formation of 25-Hydroxyvitamin D3-3-O-Sulfate, a Major Circulating Vitamin D Metabolite in Humans","volume":"46","author":"Wong","year":"2018","journal-title":"Drug Metab. Dispos."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/nrd4534","article-title":"Unleashing the Therapeutic Potential of Human Kallikrein-Related Serine Proteases","volume":"14","author":"Prassas","year":"2015","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.abb.2011.11.003","article-title":"25-Hydroxyvitamin D-24-Hydroxylase (CYP24A1): Its Important Role in the Degradation of Vitamin D","volume":"523","author":"Jones","year":"2012","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"A234","DOI":"10.1210\/jendso\/bvab048.476","article-title":"Importance of Extra-Renal CYP24A1 Expression for Maintaining Mineral Homeostasis","volume":"5","author":"Shi","year":"2021","journal-title":"J. Endocr. Soc."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"12261","DOI":"10.1038\/s41598-017-12434-z","article-title":"Group III Phospholipase A2 Promotes Colitis and Colorectal Cancer","volume":"7","author":"Murase","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.3945\/ajcn.2010.30176","article-title":"Heritability and Seasonal Variability of Vitamin D Concentrations in Male Twins","volume":"92","author":"Karohl","year":"2010","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"3381","DOI":"10.1210\/jc.2007-2702","article-title":"Genetic and Environmental Determinants of 25-Hydroxyvitamin D and 1,25-Dihydroxyvitamin D Levels in Hispanic and African Americans","volume":"93","author":"Engelman","year":"2008","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3436","DOI":"10.1016\/j.clnu.2020.11.019","article-title":"Differences and Determinants of Vitamin D Deficiency among UK Biobank Participants: A Cross-Ethnic and Socioeconomic Study","volume":"40","author":"Sutherland","year":"2021","journal-title":"Clin. Nutr."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"5483","DOI":"10.1210\/jc.2019-00630","article-title":"Genetic Variation of the Vitamin D Binding Protein Affects Vitamin D Status and Response to Supplementation in Infants","volume":"104","author":"Koljonen","year":"2019","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"218","DOI":"10.3945\/ajcn.114.092148","article-title":"Common Variants in CYP2R1 and GC Genes Are Both Determinants of Serum 25-Hydroxyvitamin D Concentrations after UVB Irradiation and after Consumption of Vitamin D\u2083-Fortified Bread and Milk during Winter in Denmark","volume":"101","author":"Nissen","year":"2015","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"413","DOI":"10.1007\/s12263-014-0413-7","article-title":"Real-Life Use of Vitamin D3-Fortified Bread and Milk during a Winter Season: The Effects of CYP2R1 and GC Genes on 25-Hydroxyvitamin D Concentrations in Danish Families, the VitmaD Study","volume":"9","author":"Nissen","year":"2014","journal-title":"Genes Nutr."},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Frost, P. (2022). The Problem of Vitamin D Scarcity: Cultural and Genetic Solutions by Indigenous Arctic and Tropical Peoples. Nutrients, 14.","DOI":"10.3390\/nu14194071"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"k601","DOI":"10.1136\/bmj.k601","article-title":"Reading Mendelian Randomisation Studies: A Guide, Glossary, and Checklist for Clinicians","volume":"362","author":"Davies","year":"2018","journal-title":"BMJ"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.2","article-title":"Guidelines for Performing Mendelian Randomization Investigations [Version 2; Peer Review: 2 Approved]","volume":"4","author":"Burgess","year":"2020","journal-title":"Wellcome Open Res."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Mokry, L.E., Ross, S., Ahmad, O.S., Forgetta, V., Smith, G.D., Leong, A., Greenwood, C.M.T., Thanassoulis, G., and Richards, J.B. (2015). Vitamin D and Risk of Multiple Sclerosis: A Mendelian Randomization Study. PLOS Med., 12.","DOI":"10.1371\/journal.pmed.1001866"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Lu, L., Bennett, D.A., Millwood, I.Y., Parish, S., McCarthy, M.I., Mahajan, A., Lin, X., Bragg, F., Guo, Y., and Holmes, M.V. (2018). Association of Vitamin D with Risk of Type 2 Diabetes: A Mendelian Randomisation Study in European and Chinese Adults. PLOS Med., 15.","DOI":"10.1371\/journal.pmed.1002566"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/S2213-8587(14)70113-5","article-title":"Association of Vitamin D Status with Arterial Blood Pressure and Hypertension Risk: A Mendelian Randomisation Study","volume":"2","author":"Vimaleswaran","year":"2014","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.1001\/jama.2011.383","article-title":"A Potential Design Flaw of Randomized Trials of Vitamin Supplements","volume":"305","author":"Morris","year":"2011","journal-title":"JAMA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1016\/j.jsbmb.2017.06.006","article-title":"Limitations of Vitamin D Supplementation Trials: Why Observational Studies Will Continue to Help Determine the Role of Vitamin D in Health","volume":"177","author":"Scragg","year":"2018","journal-title":"J. Steroid Biochem. Mol. Biol."},{"key":"ref_98","doi-asserted-by":"crossref","unstructured":"Sutherland, J.P., Zhou, A., and Hypp\u00f6nen, E. (2022). Vitamin D Deficiency Increases Mortality Risk in the UK Biobank: A Non-Linear Mendelian Randomization Study. Ann. Intern. Med., in press.","DOI":"10.7326\/M21-3324"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1016\/S2213-8587(21)00263-1","article-title":"Estimating Dose-Response Relationships for Vitamin D with Coronary Heart Disease, Stroke, and All-Cause Mortality: Observational and Mendelian Randomisation Analyses","volume":"9","author":"Sofianopoulou","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"nqac107","DOI":"10.1093\/ajcn\/nqac107","article-title":"Vitamin D and Brain Health: An Observational and Mendelian Randomization Study","volume":"116","author":"Navale","year":"2022","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"2567","DOI":"10.1212\/WNL.0000000000003430","article-title":"Genetically Decreased Vitamin D and Risk of Alzheimer Disease","volume":"87","author":"Mokry","year":"2016","journal-title":"Neurology"},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"609","DOI":"10.3233\/JAD-190713","article-title":"Circulating Vitamin D Levels and Alzheimer\u2019s Disease: A Mendelian Randomization Study in the IGAP and UK Biobank","volume":"73","author":"Wang","year":"2020","journal-title":"J. Alzheimers Dis. JAD"},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"j5375","DOI":"10.1136\/bmj.j5375","article-title":"Modifiable Pathways in Alzheimer\u2019s Disease: Mendelian Randomisation Analysis","volume":"359","author":"Larsson","year":"2017","journal-title":"BMJ"},{"key":"ref_104","doi-asserted-by":"crossref","unstructured":"Bjelakovic, G., Gluud, L.L., Nikolova, D., Whitfield, K., Wetterslev, J., Simonetti, R.G., Bjelakovic, M., and Gluud, C. (2014). Vitamin D Supplementation for Prevention of Mortality in Adults. Cochrane Database Syst. Rev., CD007470.","DOI":"10.1002\/14651858.CD007470.pub3"}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/20\/4408\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:58:16Z","timestamp":1760144296000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/14\/20\/4408"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,10,20]]},"references-count":104,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2022,10]]}},"alternative-id":["nu14204408"],"URL":"https:\/\/doi.org\/10.3390\/nu14204408","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,10,20]]}}}