{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,8]],"date-time":"2026-07-08T23:26:04Z","timestamp":1783553164658,"version":"3.55.0"},"reference-count":62,"publisher":"Cambridge University Press (CUP)","issue":"2","license":[{"start":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T00:00:00Z","timestamp":1713744000000},"content-version":"unspecified","delay-in-days":21,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["cambridge.org"],"crossmark-restriction":true},"short-container-title":["Twin Res Hum Genet"],"published-print":{"date-parts":[[2024,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>While it is known that vitamin D deficiency is associated with adverse bone outcomes, it remains unclear whether low vitamin D status may increase the risk of a wider range of health outcomes. We had the opportunity to explore the association between common genetic variants associated with both 25 hydroxyvitamin D (25OHD) and the vitamin D binding protein (DBP, encoded by the <jats:italic>GC<\/jats:italic> gene) with a comprehensive range of health disorders and laboratory tests in a large academic medical center. We used summary statistics for 25OHD and DBP to generate polygenic scores (PGS) for 66,482 participants with primarily European ancestry and 13,285 participants with primarily African ancestry from the Vanderbilt University Medical Center Biobank (BioVU). We examined the predictive properties of PGS<jats:sub>25OHD<\/jats:sub>, and two scores related to DBP concentration with respect to 1322 health-related phenotypes and 315 laboratory-measured phenotypes from electronic health records. In those with European ancestry: (a) the PGS<jats:sub>25OHD<\/jats:sub> and PGS<jats:sub>DBP<\/jats:sub> scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS<jats:sub>25OHD<\/jats:sub> was associated with decreased concentrations of triglycerides and cholesterol, and reduced risks of vitamin D deficiency, disorders of lipid metabolism, and diabetes. In general, the findings for the African ancestry group were consistent with findings from the European ancestry analyses. Our study confirms the utility of PGS and two key variants within the <jats:italic>GC<\/jats:italic> gene (rs4588 and rs7041) to predict the risk of vitamin D deficiency in clinical settings and highlights the shared biology between vitamin D-related genetic pathways a range of health outcomes.<\/jats:p>","DOI":"10.1017\/thg.2024.19","type":"journal-article","created":{"date-parts":[[2024,4,22]],"date-time":"2024-04-22T06:52:47Z","timestamp":1713768767000},"page":"69-79","update-policy":"https:\/\/doi.org\/10.1017\/policypage","source":"Crossref","is-referenced-by-count":2,"title":["Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration"],"prefix":"10.1017","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0427-7974","authenticated-orcid":false,"given":"Hailey 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Published by Cambridge University Press on behalf of International Society for Twin Studies","name":"copyright","label":"Copyright","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This is an Open Access article, distributed under the terms of the Creative Commons Attribution licence (http:\/\/creativecommons.org\/licenses\/by\/4.0\/), which permits unrestricted re-use, distribution and reproduction, provided the original article is properly cited.","name":"license","label":"License","group":{"name":"copyright_and_licensing","label":"Copyright and Licensing"}},{"value":"This content has been made available to all.","name":"free","label":"Free to read"}]}}