Document Detail


Biological pathway-based genome-wide association analysis identified the vasoactive intestinal peptide (VIP) pathway important for obesity.
MedLine Citation:
PMID:  20379146     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Recent genome-wide association (GWA) studies have identified a number of novel genes/variants predisposing to obesity. However, most GWA studies have focused on individual single-nucleotide polymorphism (SNPs)/genes with a strong statistical association with a phenotypic trait without considering potential biological interplay of the tested genes. In this study, we performed biological pathway-based GWA analysis for BMI and body fat mass. We used individual level genotype data generated from 1,000 unrelated US whites that were genotyped for ~500,000 SNPs. Statistical analysis of pathways was performed using a modification of the Gene Set Enrichment Algorithm. A total of 963 pathways extracted from the BioCarta, Kyoto Encyclopedia of Genes and Genomes (KEGG), Ambion GeneAssist, and Gene Ontology (GO) databases were analyzed. Among all of the pathways analyzed, the vasoactive intestinal peptide (VIP) pathway was most strongly associated with fat mass (nominal P = 0.0009) and was the third most strongly associated pathway with BMI (nominal P = 0.0006). After multiple testing correction, the VIP pathway achieved false-discovery rate (FDR) q values of 0.042 and 0.120 for fat mass and BMI, respectively. Our study is the first to demonstrate that the VIP pathway may play an important role in development of obesity. The study also highlights the importance of pathway-based GWA analysis in identification of additional genes/variants for complex human diseases.
Authors:
Yong-Jun Liu; Yan-Fang Guo; Li-Shu Zhang; Yu-Fang Pei; Na Yu; Ping Yu; Christopher J Papasian; Hong-Wen Deng
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-04-08
Journal Detail:
Title:  Obesity (Silver Spring, Md.)     Volume:  18     ISSN:  1930-739X     ISO Abbreviation:  Obesity (Silver Spring)     Publication Date:  2010 Dec 
Date Detail:
Created Date:  2010-11-24     Completed Date:  2011-06-07     Revised Date:  2013-05-29    
Medline Journal Info:
Nlm Unique ID:  101264860     Medline TA:  Obesity (Silver Spring)     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2339-46     Citation Subset:  IM    
Affiliation:
University of Missouri - Kansas City, School of Medicine, Kansas City, Missouri, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipose Tissue*
Adult
Aged
Body Mass Index*
Databases, Factual
European Continental Ancestry Group
Female
Genome-Wide Association Study / methods*
Genotype
Humans
Male
Middle Aged
Obesity / genetics*
Polymorphism, Single Nucleotide*
Signal Transduction / genetics
United States
Vasoactive Intestinal Peptide / genetics*
Grant Support
ID/Acronym/Agency:
P50 AR055081/AR/NIAMS NIH HHS; P50 AR055081-030001/AR/NIAMS NIH HHS; R01 AG026564-04/AG/NIA NIH HHS; R01 AR050496-06A1/AR/NIAMS NIH HHS; R01AG026564/AG/NIA NIH HHS; R01AR050496/AR/NIAMS NIH HHS; R01AR057049/AR/NIAMS NIH HHS; R03TW008221/TW/FIC NIH HHS; R21AA015973/AA/NIAAA NIH HHS; R21AG027110/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
37221-79-7/Vasoactive Intestinal Peptide
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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