Exploring the genetic architecture of circulating 25-hydroxyvitamin D.
Genet Epidemiol
; 37(1): 92-8, 2013 Jan.
Article
em En
| MEDLINE
| ID: mdl-23135809
ABSTRACT
The primary circulating form of vitamin D is 25-hydroxy vitamin D (25(OH)D), a modifiable trait linked with a growing number of chronic diseases. In addition to environmental determinants of 25(OH)D, including dietary sources and skin ultraviolet B (UVB) exposure, twin- and family-based studies suggest that genetics contribute substantially to vitamin D variability with heritability estimates ranging from 43% to 80%. Genome-wide association studies (GWAS) have identified single nucleotide polymorphisms (SNPs) located in four gene regions associated with 25(OH)D. These SNPs collectively explain only a fraction of the heritability in 25(OH)D estimated by twin- and family-based studies. Using 25(OH)D concentrations and GWAS data on 5,575 subjects drawn from five cohorts, we hypothesized that genome-wide data, in the form of (1) a polygenic score comprised of hundreds or thousands of SNPs that do not individually reach GWAS significance, or (2) a linear mixed model for genome-wide complex trait analysis, would explain variance in measured circulating 25(OH)D beyond that explained by known genome-wide significant 25(OH)D-associated SNPs. GWAS identified SNPs explained 5.2% of the variation in circulating 25(OH)D in these samples and there was little evidence additional markers significantly improved predictive ability. On average, a polygenic score comprised of GWAS-identified SNPs explained a larger proportion of variation in circulating 25(OH)D than scores comprised of thousands of SNPs that were on average, nonsignificant. Employing a linear mixed model for genome-wide complex trait analysis explained little additional variability (range 0-22%). The absence of a significant polygenic effect in this relatively large sample suggests an oligogenetic architecture for 25(OH)D.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vitamina D
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Herança Multifatorial
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Polimorfismo de Nucleotídeo Único
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Estudo de Associação Genômica Ampla
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Modelos Genéticos
Tipo de estudo:
Observational_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article