title: QTL-based association analyses reveal novel genes influencing pleiotropy of metabolic syndrome (MetS).
abstract: OBJECTIVE
  Metabolic Syndrome (MetS) is a phenotype cluster predisposing to type 2 diabetes and cardiovascular disease. We conducted a study to elucidate the genetic basis underlying linkage signals for multiple representative traits of MetS that we had previously identified at two significant QTLs on chromosomes 3q27 and 17p12.
  
  
  METHODS
  We performed QTL-specific genomic and transcriptomic analyses in 1,137 individuals from 85 extended families that contributed to the original linkage. We tested in SOLAR association of MetS phenotypes with QTL-specific haplotype-tagging SNPs as well as transcriptional profiles of peripheral blood mononuclear cells (PBMCs).
  
  
  RESULTS
  SNPs significantly associated with MetS phenotypes under the prior hypothesis of linkage mapped to seven genes at 3q27 and seven at 17p12. Prioritization based on biologic relevance, SNP association, and expression analyses identified two genes: insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) at 3q27 and tumor necrosis factor receptor 13B (TNFRSF13B) at 17p12. Prioritized genes could influence cell-cell adhesion and adipocyte differentiation, insulin/glucose responsiveness, cytokine effectiveness, plasma lipid levels, and lipoprotein densities.
  
  
  CONCLUSIONS
  Using an approach combining genomic, transcriptomic, and bioinformatic data we identified novel candidate genes for MetS.
authors: TOPS Obesity and Metabolic Research Center, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA; Human and Molecular Genetics Center, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
authors: Y
authors: Y
authors: Zhang
authors: J W
authors: JW
authors: Kent
authors: M
authors: M
authors: Olivier
authors: O
authors: O
authors: Ali
authors: U
authors: U
authors: Broeckel
authors: R M
authors: RM
authors: Abdou
authors: T D
authors: TD
authors: Dyer
authors: A
authors: A
authors: Comuzzie
authors: J E
authors: JE
authors: Curran
authors: M A
authors: MA
authors: Carless
authors: D L
authors: DL
authors: Rainwater
authors: H H H
authors: HH
authors: Göring
authors: J
authors: J
authors: Blangero
authors: A H
authors: AH
authors: Kissebah
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D002448:Cell Adhesion; D002454:Cell Differentiation; D002877:Chromosomes, Human / Q000235:genetics / Q000378:metabolism; D015331:Cohort Studies; D019295:Computational Biology; D005260:Female; D020869:Gene Expression Profiling; D056726:Genetic Association Studies; D008040:Genetic Linkage; D058685:Genetic Pleiotropy; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016601:RNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism; D055815:Young Adult
chemical_list: C498779:IGF2BP2 protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; C108467:TNFRSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein