How Can We Explain Very Low Odds Ratios in GWAS? I. Polygenic Models.
Hum Hered
; 81(4): 173-180, 2016.
Article
em En
| MEDLINE
| ID: mdl-28171865
ABSTRACT
Genome-wide association studies of common diseases often identify a number of disease-related SNPs that reach highly significant p values but at the same time show very low disease odds ratios (ORs), most <1.5 and many <1.2. Despite their statistical significance, associations involving very low ORs explain little about the genetic contribution to the disease and nothing about disease inheritance. A commonly accepted explanation for very low ORs involves a model of polygenic inheritance, i.e., where the disease being studied is caused by a large number of interacting genes, each gene contributing only a small increment to disease risk. Here we demonstrate the perhaps counterintuitive result that, within a reasonable range of disease population prevalences (≤10%), a pure polygenic model is incompatible with very low ORs, unless very large numbers (hundreds or even thousands) of polygenic loci are involved.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Razão de Chances
/
Estudo de Associação Genômica Ampla
/
Modelos Genéticos
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Humans
Idioma:
En
Revista:
Hum Hered
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Estados Unidos