title: Landscape of the relationship between type 2 diabetes and coronary heart disease through an integrated gene network analysis.
abstract: Type 2 diabetes (T2D) and coronary artery disease (CAD) are closely related chronic diseases with high prevalence and morbidity. However, a comprehensive comparison of the two diseases is lacking. Recent genome-wide association studies (GWAS) have identified a handful of single nucleotide polymorphisms (SNPs) that are significantly associated with the risk of T2D and CAD. These most significant findings may help interpret the pathogenesis of T2D and CAD. However, tremendous results from these GWAS are ignored. Here we revisited the raw datasets of these GWAS and performed an integrated gene network analysis to unveil the relationship between T2D and CAD by combining multiple datasets including protein-protein interaction (PPI) database, publication libraries, and pathway datasets. Our results showed that majority of genes were involved in the first module (1122 genes in T2D and 895 in CAD). Four pathways were found to be common in both T2D and CAD, including regulation of actin cytoskeleton, calcium signaling pathway, MAPK signaling pathway and focal adhesion (all P<0.00001). MAX which was involved in small cell lung cancer pathway was a hub gene unique to T2D (OR=1.2, P=0.006) but not in CAD. In contrast, three hub genes including PLEKHG5 (T2D: OR=1, P=1; CAD: OR=1.12, P=0.006), TIAM1 (T2D: OR=1, P=1; CAD: OR=1.48, P=0.004) and AKAP13 (T2D: OR=1, P=1; CAD: OR=1.38, P=0.001) were hub genes unique to CAD. Moreover, for some hub genes (such as SMAD3) that were susceptible to both T2D and CAD, their associated polymorphisms were unique to each of the two diseases. Our findings might provide a landscape of the relationship between T2D and CAD.
authors: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China. Electronic address: dongchangzheng@nbu.edu.cn.
authors: Changzheng
authors: C
authors: Dong
authors: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors: Linlin
authors: L
authors: Tang
authors: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors: Zhifang
authors: Z
authors: Liu
authors: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors: Shizhong
authors: S
authors: Bu
authors: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors: Qiong
authors: Q
authors: Liu
authors: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang, China.
authors: Qinwen
authors: Q
authors: Wang
authors: The Affiliated Hospital, Ningbo University, Ningbo, Zhejiang, China.
authors: Yifeng
authors: Y
authors: Mai
authors: Institute of Hypertension and Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: dwwang@tjh.tjmu.edu.cn.
authors: Dao Wen
authors: DW
authors: Wang
authors: Zhejiang Provincial Key Laboratory of Pathophysiology, School of Medicine, Ningbo University, Ningbo, Zhejiang, China; Diabetes Center, School of Medicine, Ningbo University, Ningbo, Zhejiang, China. Electronic address: duanshiwei@nbu.edu.cn.
authors: Shiwei
authors: S
authors: Duan
mesh_terms: D054758:A Kinase Anchor Proteins / Q000235:genetics; D008841:Actin Cytoskeleton / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors / Q000235:genetics; D020013:Calcium Signaling / Q000235:genetics; D003327:Coronary Disease / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D022001:Focal Adhesions / Q000235:genetics; D053263:Gene Regulatory Networks / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D020662:Guanine Nucleotide Exchange Factors / Q000235:genetics; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics; D015778:Minor Histocompatibility Antigens; D020641:Polymorphism, Single Nucleotide; D025941:Protein Interaction Mapping; D011518:Proto-Oncogene Proteins / Q000235:genetics; D051900:Smad3 Protein / Q000235:genetics; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1
chemical_list: D054758:A Kinase Anchor Proteins; C085467:AKAP13 protein, human; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D020662:Guanine Nucleotide Exchange Factors; C499330:MAX protein, human; D015778:Minor Histocompatibility Antigens; C522397:PLEKHG5 protein, human; D011518:Proto-Oncogene Proteins; C497790:SMAD3 protein, human; D051900:Smad3 Protein; D000075684:T-Lymphoma Invasion and Metastasis-inducing Protein 1; C087334:TIAM1 protein, human
keywords: Coronary artery disease; Genome-wide association; Hub; Network analysis; Pathway; Protein–protein interaction; Type 2 diabetes