title: Differential coexpression analysis of obesity-associated networks in human subcutaneous adipose tissue.
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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Genomics of Common Disease, School of Public Health, Imperial College London, Hammersmith Hospital, London, UK.
authors.forename: A J
authors.initials: AJ
authors.lastname: Walley
authors.forename: P
authors.initials: P
authors.lastname: Jacobson
authors.forename: M
authors.initials: M
authors.lastname: Falchi
authors.forename: L
authors.initials: L
authors.lastname: Bottolo
authors.forename: J C
authors.initials: JC
authors.lastname: Andersson
authors.forename: E
authors.initials: E
authors.lastname: Petretto
authors.forename: A
authors.initials: A
authors.lastname: Bonnefond
authors.forename: E
authors.initials: E
authors.lastname: Vaillant
authors.forename: C
authors.initials: C
authors.lastname: Lecoeur
authors.forename: V
authors.initials: V
authors.lastname: Vatin
authors.forename: M
authors.initials: M
authors.lastname: Jernas
authors.forename: D
authors.initials: D
authors.lastname: Balding
authors.forename: M
authors.initials: M
authors.lastname: Petteni
authors.forename: Y S
authors.initials: YS
authors.lastname: Park
authors.forename: T
authors.initials: T
authors.lastname: Aitman
authors.forename: S
authors.initials: S
authors.lastname: Richardson
authors.forename: L
authors.initials: L
authors.lastname: Sjostrom
authors.forename: L M S
authors.initials: LM
authors.lastname: Carlsson
authors.forename: P
authors.initials: P
authors.lastname: Froguel
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D015992:Body Mass Index; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D015816:Cell Adhesion Molecules, Neuronal / Q000235:genetics / Q000378:metabolism*; D015331:Cohort Studies; D005260:Female; D058851:GPI-Linked Proteins / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D008040:Genetic Linkage; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000453:epidemiology / Q000235:genetics* / Q000378:metabolism*; D040081:Protein Array Analysis; D040641:Quantitative Trait Loci; D060888:Real-Time Polymerase Chain Reaction; D035781:Siblings; D050151:Subcutaneous Fat / Q000378:metabolism*; D013548:Sweden / Q000453:epidemiology; D013851:Thinness / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015815:Cell Adhesion Molecules; D015816:Cell Adhesion Molecules, Neuronal; D058851:GPI-Linked Proteins; C485559:NEGR1 protein, human