A Genome-Wide Association Study and Complex Network Identify Four Core Hub Genes in Bipolar Disorder

Zengyan Xie; Xianyan Yang; Xiaoya Deng; Mingyue Ma; Kunxian Shu

doi:10.3390/ijms18122763

A Genome-Wide Association Study and Complex Network Identify Four Core Hub Genes in Bipolar Disorder

Int J Mol Sci. 2017 Dec 19;18(12):2763. doi: 10.3390/ijms18122763.

Authors

Zengyan Xie¹, Xianyan Yang², Xiaoya Deng³, Mingyue Ma⁴, Kunxian Shu⁵

Affiliations

¹ Institute of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China. xiezy@cqupt.edu.cn.
² Institute of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China. yxianyan@outlook.com.
³ Institute of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China. deng_xiaoya@outlook.com.
⁴ Institute of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China. mamingyue@cqupt.edu.cn.
⁵ Institute of Bioinformatics, Chongqing University of Posts and Telecommunications, Chongqing 400065, China. shukx@cqupt.edu.cn.

Abstract

Bipolar disorder is a common and severe mental illness with unsolved pathophysiology. A genome-wide association study (GWAS) has been used to find a number of risk genes, but it is difficult for a GWAS to find genes indirectly associated with a disease. To find core hub genes, we introduce a network analysis after the GWAS was conducted. Six thousand four hundred fifty eight single nucleotide polymorphisms (SNPs) with p < 0.01 were sifted out from Wellcome Trust Case Control Consortium (WTCCC) dataset and mapped to 2045 genes, which are then compared with the protein-protein network. One hundred twelve genes with a degree >17 were chosen as hub genes from which five significant modules and four core hub genes (FBXL13, WDFY2, bFGF, and MTHFD1L) were found. These core hub genes have not been reported to be directly associated with BD but may function by interacting with genes directly related to BD. Our method engenders new thoughts on finding genes indirectly associated with, but important for, complex diseases.

Keywords: GWAS; bipolar disorder; functional enrichment analysis; network analysis.

MeSH terms

Bipolar Disorder / genetics*
F-Box Proteins / genetics
Fibroblast Growth Factors / genetics
Gene Regulatory Networks*
Genome-Wide Association Study
Humans
Intracellular Signaling Peptides and Proteins / genetics
Methylenetetrahydrofolate Dehydrogenase (NADP) / genetics
Minor Histocompatibility Antigens / genetics
Polymorphism, Single Nucleotide*

Substances

F-Box Proteins
Intracellular Signaling Peptides and Proteins
Minor Histocompatibility Antigens
WDFY2 protein, human
Fibroblast Growth Factors
MTHFD1 protein, human
Methylenetetrahydrofolate Dehydrogenase (NADP)