title: Genetic and environmental factors are associated with serum 25-hydroxyvitamin D concentrations in older African Americans.
abstract: BACKGROUND
  Low circulating 25-hydroxyvitamin D [25(OH)D] is prevalent in African Americans, but predictors of vitamin D status are understudied compared to Caucasian populations.
  
  
  OBJECTIVE
  We investigated whether certain environmental and genetic factors are predictors of circulating 25(OH)D in 989 elderly African Americans participating in the Health, Aging, and Body Composition (Health ABC) Study.
  
  
  METHODS
  Regression analysis estimated the cross-sectional association of nongenetic (environmental) factors with 25(OH)D. Single nucleotide polymorphisms (SNPs) associated with 25(OH)D in Caucasian genome-wide association studies (GWASs) were analyzed for association with serum 25(OH)D, including analyses of all imputed SNPs in identified genomic regions. Genome-wide complex trait analysis (GCTA) evaluated the association of all (genome-wide) genotyped SNPs with serum 25(OH)D in the Health ABC Study with replication in the Multi-Ethnic Study of Atherosclerosis (MESA) cohort.
  
  
  RESULTS
  Gender, study site, season of blood draw, body mass index, dietary supplement use, dairy and cereal consumption, Healthy Eating Index score, and walking >180 min/wk were associated with 25(OH)D (P < 0.05), jointly explaining 25% of the variation in circulating 25(OH)D. Multivitamin supplement use was the strongest predictor of circulating 25(OH)D, and supplement users had a 6.3-μg/L higher serum 25(OH)D concentration compared with nonusers. Previous GWAS-identified gene regions were not replicated in African Americans, but the nonsynonymous rs7041 SNP in group-specific component (vitamin D binding protein) was close to significance thresholds (P = 0.08), and there was evidence for an interaction between this SNP and use of multivitamin supplements in relation to serum 25(OH)D concentration (P = 0.04). Twenty-three percent (95% CI: 0%, 52%) of the variation in serum 25(OH)D was explained by total genetic variation in a pooled GCTA of 2087 Health ABC Study and MESA African-American participants, but population substructure effects could not be separated from other genetic influences.
  
  
  CONCLUSIONS
  Modifiable dietary and lifestyle predictors of serum 25(OH)D were identified in African Americans. GCTA confirms that a proportion of 25(OH)D variability is attributable to genetic variation, but genomic regions associated with the 25(OH)D phenotype identified in prior GWASs of European Americans were not replicated in the Health ABC Study in African Americans.
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY;
authors.forename: Joyanna G
authors.initials: JG
authors.lastname: Hansen
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY;
authors.forename: Wenbo
authors.initials: W
authors.lastname: Tang
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY;
authors.forename: Katie C
authors.initials: KC
authors.lastname: Hootman
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY;
authors.forename: Patsy M
authors.initials: PM
authors.lastname: Brannon
authors.affiliation: Sticht Center on Aging, and.
authors.forename: Denise K
authors.initials: DK
authors.lastname: Houston
authors.affiliation: Sticht Center on Aging, and.
authors.forename: Stephen B
authors.initials: SB
authors.lastname: Kritchevsky
authors.affiliation: Intramural Research Program, Laboratory of Epidemiology and Population Science, National Institute on Aging, NIH, Bethesda, MD;
authors.forename: Tamara B
authors.initials: TB
authors.lastname: Harris
authors.affiliation: Intramural Research Program, Laboratory of Epidemiology and Population Science, National Institute on Aging, NIH, Bethesda, MD;
authors.forename: Melissa
authors.initials: M
authors.lastname: Garcia
authors.affiliation: Department of Biostatistical Sciences and.
authors.forename: Kurt
authors.initials: K
authors.lastname: Lohman
authors.affiliation: Department of Epidemiology and Prevention, Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC;
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Division of Nephrology, Department of Medicine, and Kidney Research Institute, University of Washington, Seattle, WA;
authors.forename: Ian H
authors.initials: IH
authors.lastname: de Boer
authors.affiliation: Division of Nephrology, Department of Medicine, and Kidney Research Institute, University of Washington, Seattle, WA;
authors.forename: Bryan R
authors.initials: BR
authors.lastname: Kestenbaum
authors.affiliation: Division of Nephrology, Department of Medicine, and Kidney Research Institute, University of Washington, Seattle, WA;
authors.forename: Cassianne
authors.initials: C
authors.lastname: Robinson-Cohen
authors.affiliation: New York Academy of Medicine, New York, NY; and.
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.affiliation: Division of Nutritional Sciences, Cornell University, Ithaca, NY; Department of Healthcare Policy and Research, Division of Biostatistics and Epidemiology, Weill Cornell Medical College, New York, NY pac6@cornell.edu.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Cassano
mesh_terms: D001741:Black or African American / Q000235:genetics*; D000368:Aged; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D019587:Dietary Supplements; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012621:Seasons; D014807:Vitamin D / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000097:blood; D014808:Vitamin D Deficiency / Q000097:blood / Q000235:genetics*; D014809:Vitamin D-Binding Protein / Q000235:genetics / Q000378:metabolism; D044465:White People / Q000235:genetics
chemical_list: D014809:Vitamin D-Binding Protein; D014807:Vitamin D; C104450:25-hydroxyvitamin D
keywords: 25-hydroxyvitamin D; GC; GCTA; rs7041; supplements; vitamin D