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Phenomewide Association Study of Health Outcomes Associated With the Genetic Correlates of 25 Hydroxyvitamin D Concentration and Vitamin D Binding Protein Concentration.
Kresge, Hailey A; Blostein, Freida; Goleva, Slavina; Albiñana, Clara; Revez, Joana A; Wray, Naomi R; Vilhjálmsson, Bjarni J; Zhu, Zhihong; McGrath, John J; Davis, Lea K.
Afiliación
  • Kresge HA; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Blostein F; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Goleva S; Vanderbilt Genetics Institute, Vanderbilt University Medical Center, Nashville, TN, USA.
  • Albiñana C; National Centre for Register-Based Research, Aarhus University, Aarhus V, Denmark.
  • Revez JA; Department of Psychiatry, University of Oxford, Oxford, UK.
  • Wray NR; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
  • Vilhjálmsson BJ; Department of Psychiatry, University of Oxford, Oxford, UK.
  • Zhu Z; Institute for Molecular Bioscience, University of Queensland, Brisbane, QLD, Australia.
  • McGrath JJ; Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia.
  • Davis LK; National Centre for Register-Based Research, Aarhus University, Aarhus V, Denmark.
Twin Res Hum Genet ; 27(2): 69-79, 2024 Apr.
Article en En | MEDLINE | ID: mdl-38644690
ABSTRACT
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 GC 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 PGS25OHD, 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 PGS25OHD and PGSDBP scores, and individual SNPs rs4588 and rs7041 were associated with both 25OHD concentration and 1,25 dihydroxyvitamin D concentrations; (b) higher PGS25OHD 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 GC 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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina D / Proteína de Unión a Vitamina D Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Twin Res Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Vitamina D / Proteína de Unión a Vitamina D Límite: Adult / Aged / Female / Humans / Male / Middle aged Idioma: En Revista: Twin Res Hum Genet Asunto de la revista: GENETICA MEDICA Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Reino Unido