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Genome-wide association study (GWAS) of circulating vitamin D outcomes among individuals of African ancestry.
Parlato, Lisa A; Welch, Rene; Ong, Irene M; Long, Jirong; Cai, Qiuyin; Steinwandel, Mark D; Blot, William J; Zheng, Wei; Warren Andersen, Shaneda.
Afiliação
  • Parlato LA; Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA.
  • Welch R; Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; University of Wisconsin Carbone Cancer Center, Madison, WI, USA; Department of Obstetrics and Gynecology, UW-Health Hospital, University of Wisconsin-Madison,
  • Ong IM; Department of Biostatistics and Medical Informatics, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; University of Wisconsin Carbone Cancer Center, Madison, WI, USA; Department of Obstetrics and Gynecology, UW-Health Hospital, University of Wisconsin-Madison,
  • Long J; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Cai Q; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Steinwandel MD; International Epidemiology Field Station, Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
  • Blot WJ; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA; International Epidemiology Field Station, Vanderbilt Institute for Clinical and Translational Research, Nashville, TN, USA.
  • Zheng W; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Cancer Center, Vanderbilt University School of Medicine, Nashville, TN, USA.
  • Warren Andersen S; Department of Population Health Sciences, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA; University of Wisconsin Carbone Cancer Center, Madison, WI, USA; Division of Epidemiology, Department of Medicine, Vanderbilt Epidemiology Center, Vanderbilt-Ingram Canc
Am J Clin Nutr ; 117(2): 308-316, 2023 02.
Article em En | MEDLINE | ID: mdl-36811574
BACKGROUND: Vitamin D deficiency is more common among African-ancestry individuals and may be associated with adverse health outcomes. Vitamin D binding protein (VDBP) regulates concentrations of biologically active vitamin D. OBJECTIVE: We conducted genome-wide association study (GWAS) of VDBP and 25-hydroxyvitamin D among African-ancestry individuals. METHODS: Data were collected from 2,602 African American adults from the Southern Community Cohort Study (SCCS) and 6,934 African- or Caribbean-ancestry adults from the UK Biobank. Serum VDBP concentrations were available only in the SCCS and were measured by using the Polyclonal Human VDBP ELISA kit. Serum 25-hydroxyvitamin D concentrations for both study samples were measured by using Diasorin Liason, a chemiluminescent immunoassay. Participants were genotyped for single nucleotide polymorphisms (SNPs) with genome-wide coverage by using Illumina or Affymetrix platforms. Fine-mapping analysis was performed by using forward stepwise linear regression models including all variants with P value < 5 × 10-8 and within 250 kbps of a lead SNP. RESULTS: We identified 4 loci notably associated with VDBP concentrations in the SCCS population: rs7041 (per allele ß = 0.61 µg/mL, SE = 0.05, P = 1.4 × 10-48) and rs842998 (per allele ß = 0.39 µg/mL, SE = 0.03, P = 4.0 × 10-31) in GC, rs8427873 (per allele ß = 0.31 µg/mL, SE = 0.04, P = 3.0 × 10-14) near GC and rs11731496 (per allele ß = 0.21 µg/mL, SE = 0.03, P = 3.6 × 10-11) in between GC and NPFFR2. In conditional analyses, which included the above-mentioned SNPs, only rs7041 remained notable (P = 4.1 × 10-21). SNP rs4588 in GC was the only GWAS-identified SNP associated with 25-hydroxyvitamin D concentration. Among UK Biobank participants: per allele ß = -0.11 µg/mL, SE = 0.01, P = 1.5 × 10-13; in the SCCS: per allele ß = -0.12 µg/mL, SE = 0.06, P = 2.8 × 10-02). rs7041 and rs4588 are functional SNPs that influence the binding affinity of VDBP to 25-hydroxyvitamin D. CONCLUSIONS: Our results were in line with previous studies conducted in European-ancestry populations, showing that GC, the gene that directly encodes for VDBP, would be important for VDBP and 25-hydroxyvitamin D concentrations. The current study extends our knowledge of the genetics of vitamin D in diverse populations.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Deficiência de Vitamina D / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Humans Idioma: En Revista: Am J Clin Nutr Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Deficiência de Vitamina D / Estudo de Associação Genômica Ampla Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Limite: Adult / Humans Idioma: En Revista: Am J Clin Nutr Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Estados Unidos