Comparing strategies to fine-map the association of common SNPs at chromosome 9p21 with type 2 diabetes and myocardial infarction.
Nat Genet
; 43(8): 801-5, 2011 Jul 24.
Article
em En
| MEDLINE
| ID: mdl-21775993
ABSTRACT
Noncoding variants at human chromosome 9p21 near CDKN2A and CDKN2B are associated with type 2 diabetes, myocardial infarction, aneurysm, vertical cup disc ratio and at least five cancers. Here we compare approaches to more comprehensively assess genetic variation in the region. We carried out targeted sequencing at high coverage in 47 individuals and compared the results to pilot data from the 1000 Genomes Project. We imputed variants into type 2 diabetes and myocardial infarction cohorts directly from targeted sequencing, from a genotyped reference panel derived from sequencing and from 1000 Genomes Project low-coverage data. Polymorphisms with frequency >5% were captured well by all strategies. Imputation of intermediate-frequency polymorphisms required a higher density of tag SNPs in disease samples than is available on first-generation genome-wide association study (GWAS) arrays. Our association analyses identified more comprehensive sets of variants showing equivalent statistical association with type 2 diabetes or myocardial infarction, but did not identify stronger associations than the original GWAS signals.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Variação Genética
/
Cromossomos Humanos Par 9
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Mapeamento Cromossômico
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Polimorfismo de Nucleotídeo Único
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Diabetes Mellitus Tipo 2
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Estudo de Associação Genômica Ampla
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Infarto do Miocárdio
Tipo de estudo:
Risk_factors_studies
Limite:
Humans
Idioma:
En
Revista:
Nat Genet
Assunto da revista:
GENETICA MEDICA
Ano de publicação:
2011
Tipo de documento:
Article
País de afiliação:
Estados Unidos