Common variants conferring risk of schizophrenia: a pathway analysis of GWAS data.
Unlike the typical analysis of single markers in genome-wide association studies (GWAS), we incorporated Gene Set Enrichment Analysis (GSEA) and hypergeometric test and combined them using Fisher's combined method to perform pathway-based analysis in order to detect genes' combined effects on mediating schizophrenia. A few pathways were consistently found to be top ranked and likely associated with schizophrenia by these methods; they are related to metabolism of glutamate, the process of apoptosis, inflammation, and immune system (e.g., glutamate metabolism pathway, TGF-beta signaling pathway, and TNFR1 pathway). The genes involved in these pathways had not been detected by single marker analysis, suggesting this approach may complement the original analysis of GWAS dataset.
Jia
Peilin
P
Department of Biomedical Informatics, Vanderbilt University School of Medicine, Nashville, TN 37232, USA.
Wang
Lily
L
Meltzer
Herbert Y
HY
Zhao
Zhongming
Z
D020022:Genetic Predisposition to Disease; D014644:Genetic Variation / Q000235:genetics*; D055106:Genome-Wide Association Study; D018698:Glutamic Acid / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D012559:Schizophrenia / Q000235:genetics*; D015398:Signal Transduction / Q000235:genetics*
D018698:Glutamic Acid