QTL-based association analyses reveal novel genes influencing pleiotropy of metabolic syndrome (MetS). Obesity (Silver Spring) 2013 Oct;21(10):2099-111
Date
02/19/2013Pubmed ID
23418049Pubmed Central ID
PMC3769476DOI
10.1002/oby.20324Scopus ID
2-s2.0-84885386475 (requires institutional sign-in at Scopus site) 11 CitationsAbstract
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.
DESIGN AND 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.
Author List
Zhang Y, Kent JW Jr, Olivier M, Ali O, Broeckel U, Abdou RM, Dyer TD, Comuzzie A, Curran JE, Carless MA, Rainwater DL, Göring HH, Blangero J, Kissebah AHAuthor
Ulrich Broeckel MD Chief, Center Associate Director, Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdipocytesAdult
Body Composition
Body Mass Index
Cell Adhesion
Cell Differentiation
Chromosomes, Human
Cohort Studies
Computational Biology
Female
Gene Expression Profiling
Genetic Association Studies
Genetic Linkage
Genetic Pleiotropy
Genetic Predisposition to Disease
Haplotypes
Humans
Leukocytes, Mononuclear
Male
Metabolic Syndrome
Middle Aged
Pedigree
Phenotype
Polymorphism, Single Nucleotide
Quantitative Trait Loci
RNA, Messenger
RNA-Binding Proteins
Transcriptome
Transmembrane Activator and CAML Interactor Protein
Young Adult
