Genetic architecture for susceptibility to gout in the KARE cohort study
| Autor: | Chaeyoung Lee, Minyoung Kong, Jimin Shin, Younyoung Kim |
|---|---|
| Rok vydání: | 2012 |
| Předmět: |
musculoskeletal diseases
congenital hereditary and neonatal diseases and abnormalities Gout Genome-wide association study Single-nucleotide polymorphism Regulatory Sequences Nucleic Acid Biology Polymorphism Single Nucleotide Cohort Studies chemistry.chemical_compound Republic of Korea Genetics medicine Humans Genetic Predisposition to Disease Genetics (clinical) Binding Sites nutritional and metabolic diseases medicine.disease Genetic architecture Uric Acid chemistry Genetic epidemiology Genetic Loci Statistical genetics Uric acid Pharmacogenetics |
| Zdroj: | Journal of Human Genetics. 57:379-384 |
| ISSN: | 1435-232X 1434-5161 |
| Popis: | This study aimed to identify functional associations of cis-regulatory regions with gout susceptibility using data resulted from a genome-wide association study (GWAS), and to show a genetic architecture for gout with interaction effects among genes within each of the identified functions. The GWAS was conducted with 8314 control subjects and 520 patients with gout in the Korea Association REsource cohort. However, genetic associations with any individual nucleotide variants were not discovered by Bonferroni multiple testing in the GWAS (P>1.42 × 10(-7)). Genomic regions enrichment analysis was employed to identify functional associations of cis-regulatory regions. This analysis revealed several biological processes associated with gout susceptibility, and they were quite different from those with serum uric acid level. Epistasis for susceptibility to gout was estimated using entropy decomposition with selected genes within each biological process identified by the genomic regions enrichment analysis. Some epistases among nucleotide sequence variants for gout susceptibility were found to be larger than their individual effects. This study provided the first evidence that genetic factors for gout susceptibility greatly differed from those for serum uric acid level, which may suggest that research endeavors for identifying genetic factors for gout susceptibility should not be heavily dependent on pathogenesis of uric acid. Interaction effects between genes should be examined to explain a large portion of phenotypic variability for gout susceptibility. |
| Databáze: | OpenAIRE |
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