Differential coexpression analysis of obesity-associated networks in human subcutaneous adipose tissue.
Int J Obes (Lond)
; 36(1): 137-47, 2012 Jan.
Article
de En
| MEDLINE
| ID: mdl-21427694
ABSTRACT
OBJECTIVE:
To use a unique obesity-discordant sib-pair study design to combine differential expression analysis, expression quantitative trait loci (eQTLs) mapping and a coexpression regulatory network approach in subcutaneous human adipose tissue to identify genes relevant to the obese state. STUDYDESIGN:
Genome-wide transcript expression in subcutaneous human adipose tissue was measured using Affymetrix U133 Plus 2.0 microarrays (Affymetrix, Santa Clara, CA, USA), and genome-wide genotyping data was obtained using an Applied Biosystems (Applied Biosystems; Life Technologies, Carlsbad, CA, USA) SNPlex linkage panel.SUBJECTS:
A total of 154 Swedish families ascertained through an obese proband (body mass index (BMI) >30 kg m(-2)) with a discordant sibling (BMI>10 kg m(-2) less than proband).RESULTS:
Approximately one-third of the transcripts were differentially expressed between lean and obese siblings. The cellular adhesion molecules (CAMs) KEGG grouping contained the largest number of differentially expressed genes under cis-acting genetic control. By using a novel approach to contrast CAMs coexpression networks between lean and obese siblings, a subset of differentially regulated genes was identified, with the previously GWAS obesity-associated neuronal growth regulator 1 (NEGR1) as a central hub. Independent analysis using mouse data demonstrated that this finding of NEGR1 is conserved across species.CONCLUSION:
Our data suggest that in addition to its reported role in the brain, NEGR1 is also expressed in subcutaneous adipose tissue and acts as a central 'hub' in an obesity-related transcript network.
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Maigreur
/
Molécules d'adhérence cellulaire neuronale
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Molécules d'adhérence cellulaire
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Locus de caractère quantitatif
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Graisse sous-cutanée
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Obésité
Type d'étude:
Etiology_studies
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Incidence_studies
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Observational_studies
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Prognostic_studies
/
Risk_factors_studies
Limites:
Adolescent
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Adult
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Animals
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Female
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Humans
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Male
/
Middle aged
Pays/Région comme sujet:
Europa
Langue:
En
Journal:
Int J Obes (Lond)
Sujet du journal:
METABOLISMO
Année:
2012
Type de document:
Article
Pays d'affiliation:
Royaume-Uni