Genetic Regulation of Adipose Gene Expression and Cardio-Metabolic Traits.
Am J Hum Genet
; 100(3): 428-443, 2017 Mar 02.
Article
em En
| MEDLINE
| ID: mdl-28257690
ABSTRACT
Subcutaneous adipose tissue stores excess lipids and maintains energy balance. We performed expression quantitative trait locus (eQTL) analyses by using abdominal subcutaneous adipose tissue of 770 extensively phenotyped participants of the METSIM study. We identified cis-eQTLs for 12,400 genes at a 1% false-discovery rate. Among an approximately 680 known genome-wide association study (GWAS) loci for cardio-metabolic traits, we identified 140 coincident cis-eQTLs at 109 GWAS loci, including 93 eQTLs not previously described. At 49 of these 140 eQTLs, gene expression was nominally associated (p < 0.05) with levels of the GWAS trait. The size of our dataset enabled identification of five loci associated (p < 5 × 10-8) with at least five genes located >5 Mb away. These trans-eQTL signals confirmed and extended the previously reported KLF14-mediated network to 55 target genes, validated the CIITA regulation of class II MHC genes, and identified ZNF800 as a candidate master regulator. Finally, we observed similar expression-clinical trait correlations of genes associated with GWAS loci in both humans and a panel of genetically diverse mice. These results provide candidate genes for further investigation of their potential roles in adipose biology and in regulating cardio-metabolic traits.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Doenças Cardiovasculares
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Regulação da Expressão Gênica
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Síndrome Metabólica
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Locos de Características Quantitativas
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Gordura Subcutânea
Tipo de estudo:
Prognostic_studies
Limite:
Aged
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Animals
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Am J Hum Genet
Ano de publicação:
2017
Tipo de documento:
Article
País de afiliação:
Estados Unidos