TY - JOUR
T1 - Genetic and environmental factors are associated with serum 25-hydroxyvitamin D concentrations in older African Americans
AU - Hansen, Joyanna G.
AU - Tang, Wenbo
AU - Hootman, Katie C.
AU - Brannon, Patsy M.
AU - Houston, Denise K.
AU - Kritchevsky, Stephen B.
AU - Harris, Tamara B.
AU - Garcia, Melissa
AU - Lohman, Kurt
AU - Liu, Yongmei
AU - De Boer, Ian H.
AU - Kestenbaum, Bryan R.
AU - Robinson-Cohen, Cassianne
AU - Siscovick, David S.
AU - Cassano, Patricia A.
N1 - Publisher Copyright:
© 2015 American Society for Nutrition.
PY - 2015
Y1 - 2015
N2 - 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 usewas the strongest predictor of circulating 25(OH)D, and supplement users had a 6.3-mg/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.
AB - 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 usewas the strongest predictor of circulating 25(OH)D, and supplement users had a 6.3-mg/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.
KW - 25-hydroxyvitamin D
KW - GC
KW - GCTA
KW - Rs7041
KW - Supplements
KW - Vitamin D
UR - http://www.scopus.com/inward/record.url?scp=84928541274&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84928541274&partnerID=8YFLogxK
U2 - 10.3945/jn.114.202093
DO - 10.3945/jn.114.202093
M3 - Article
C2 - 25716552
AN - SCOPUS:84928541274
SN - 0022-3166
VL - 145
SP - 799
EP - 805
JO - Journal of Nutrition
JF - Journal of Nutrition
IS - 4
ER -