講演情報
[PE2-12]GWASで同定される肥満関連SNPsの統合的機能予測
○ANG MIA YANG1,2, 竹内 史比古1, 加藤 規弘1,2 (1.国立国際医療研究センター研究所 遺伝子診断治療開発研究部, 2.東京大学医学系研究科 分子細胞生物学 臨床ゲノム情報学)
Introduction
Obesity is a multifactorial disorder, defined by excessive fat accumulation in the body. While GWAS have successfully identified a large number of susceptibility loci for obesity, the underlying mechanisms remain to be clarified.
Objective
To systematically perform functional annotation of obesity-associated SNPs detectable through GWAS.
Method
Based on publicly-available GWAS data, we performed a series of functional annotation of obesity-associated SNPs using databases with each developed for diverse purposes, i.e., RegulomeDB, CardioGxE, TWAS-hub, Expression Atlas and DisGeNET; all of these help us identify a set of genes that are important to the pathogenesis of obesity. Also, we performed pathway enrichment analysis and reconstructed protein-protein interaction (PPI) network using Enrichr and STRING databases, respectively.
Results
We collated a total of 171,726 obesity-associated SNPs, which were grouped into 1,051 unique loci. Our functional annotation identified ~100 genes, including 60 eQTL genes (e.g., ADCY3 and SPI1), 16 genes with significant gene-environment interactions (e.g., PPARG and TCF7L2), 39 TWAS genes detectable in obesity-associated tissues. Pathway enrichment analysis revealed significant GO terms, including glucose homeostasis and regulation of insulin secretion, among the functional genes thus identified. PPI network analysis further indicated energy intake and expenditure to be a principal driver of obesity.
Conclusions
The outcomes of our study provide targets and clues for future functional analyses on the pathogenesis of obesity.
Obesity is a multifactorial disorder, defined by excessive fat accumulation in the body. While GWAS have successfully identified a large number of susceptibility loci for obesity, the underlying mechanisms remain to be clarified.
Objective
To systematically perform functional annotation of obesity-associated SNPs detectable through GWAS.
Method
Based on publicly-available GWAS data, we performed a series of functional annotation of obesity-associated SNPs using databases with each developed for diverse purposes, i.e., RegulomeDB, CardioGxE, TWAS-hub, Expression Atlas and DisGeNET; all of these help us identify a set of genes that are important to the pathogenesis of obesity. Also, we performed pathway enrichment analysis and reconstructed protein-protein interaction (PPI) network using Enrichr and STRING databases, respectively.
Results
We collated a total of 171,726 obesity-associated SNPs, which were grouped into 1,051 unique loci. Our functional annotation identified ~100 genes, including 60 eQTL genes (e.g., ADCY3 and SPI1), 16 genes with significant gene-environment interactions (e.g., PPARG and TCF7L2), 39 TWAS genes detectable in obesity-associated tissues. Pathway enrichment analysis revealed significant GO terms, including glucose homeostasis and regulation of insulin secretion, among the functional genes thus identified. PPI network analysis further indicated energy intake and expenditure to be a principal driver of obesity.
Conclusions
The outcomes of our study provide targets and clues for future functional analyses on the pathogenesis of obesity.