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Nature ; 452(7186): 423-8, 2008 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-18344981

RESUMO

Common human diseases result from the interplay of many genes and environmental factors. Therefore, a more integrative biology approach is needed to unravel the complexity and causes of such diseases. To elucidate the complexity of common human diseases such as obesity, we have analysed the expression of 23,720 transcripts in large population-based blood and adipose tissue cohorts comprehensively assessed for various phenotypes, including traits related to clinical obesity. In contrast to the blood expression profiles, we observed a marked correlation between gene expression in adipose tissue and obesity-related traits. Genome-wide linkage and association mapping revealed a highly significant genetic component to gene expression traits, including a strong genetic effect of proximal (cis) signals, with 50% of the cis signals overlapping between the two tissues profiled. Here we demonstrate an extensive transcriptional network constructed from the human adipose data that exhibits significant overlap with similar network modules constructed from mouse adipose data. A core network module in humans and mice was identified that is enriched for genes involved in the inflammatory and immune response and has been found to be causally associated to obesity-related traits.


Assuntos
Perfilação da Expressão Gênica , Regulação da Expressão Gênica/genética , Obesidade/genética , Tecido Adiposo/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Sangue/metabolismo , Índice de Massa Corporal , Estudos de Coortes , Feminino , Genoma Humano , Humanos , Islândia , Escore Lod , Masculino , Camundongos , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Tamanho da Amostra , Relação Cintura-Quadril , População Branca/genética
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