MK4MDD

Genetic/Epigenetic Locus Search Cross Data Search

Study Report

Reference

Citation	Kao CF, 2012 PubMed
Full Info	Kao CF, Jia P, Zhao Z, Kuo PH. Enriched pathways for major depressive disorder identified from a genome-wide association study. Int J Neuropsychopharmacol 2012: 1-11.

Study

Hypothesis or Background	Major depressive disorder (MDD) has caused a substantial burden of disease worldwide with moderate heritability. Despite efforts through conducting numerous association studies and now, genome-wide association (GWA) studies, the success of identifying susceptibility loci for MDD has been limited, which is partially attributed to the complex nature of depression pathogenesis. A pathway-based analytic strategy to investigate the joint effects of various genes within specific biological pathways has emerged as a powerful tool for complex traits. The present study aimed to identify enriched pathways for depression using a GWA dataset for MDD.
Sample Information
Method Detail	For each gene, we estimated its gene-wise p value using combined and minimum p value, separately. Canonical pathways from the Kyoto Encyclopedia of Genes and Genomes (KEGG) and BioCarta were used. We employed four pathway-based analytic approaches (gene set enrichment analysis, hypergeometric test, sum-square statistic, sum-statistic). We adjusted for multiple testing using Benjamini & Hochberg's method to report significant pathways.
Method Keywords	pathway enrichment
Result	We found 17 significantly enriched pathways for depression, which presented low-to-intermediate crosstalk. The top four pathways were long-term depression (p1x10-5), calcium signalling (p6x10-5), arrhythmogenic right ventricular cardiomyopathy (p1.6x10-4) and cell adhesion molecules (p2.2x10-4)
Conclusions	In conclusion, our comprehensive pathway analyses identified promising pathways for depression that are related to neurotransmitter and neuronal systems, immune system and inflammatory response, which may be involved in the pathophysiological mechanisms underlying depression. We demonstrated that pathway enrichment analysis is promising to facilitate our understanding of complex traits through a deeper interpretation of GWA data. Application of this comprehensive analytic strategy in upcoming GWA data for depression could validate the findings reported in this study.

Relationships reported by Kao CF, 2012

Component A Approved Name (Name in Paper)	Component A Type	Component B Approved Name (Name in Paper)	Component B Type	Statistical Result	Relationship Description	Result Category (Positive/Negative))
MDD	syndrome	ECM-receptor interaction (ECM-receptor interaction)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Axon guidance (Axon guidance)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Vascular smooth muscle contraction (Vascular smooth muscle contraction)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	PKC-catalysed phosphorylation of inhibitory phosphoprotein of myosin phosphatase (PKC-catalysed phosphorylation of inhibitory phosphoprotein of myosin phosphatase)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	T cell receptor signalling pathway (T cell receptor signalling pathway)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	O-Glycan biosynthesis (O-Glycan biosynthesis)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	NF-kB activation by non-typable Haemophilus in?uenzae (NF-kB activation by non-typable Haemophilus in?uenzae)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Cell cycle_G1/S check point (Cell cycle_G1/S check point)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Calcium signalling pathway (Calcium signalling pathway)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Arrhythmogenic right ventricular cardiomyopathy (Arrhythmogenic right ventricular cardiomyopathy)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Cell adhesion molecules (Cell adhesion molecules)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Focal adhesion (Focal adhesion)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Type I diabetes mellitus (Type I diabetes mellitus)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Regulation of actin cytoskeleton (Regulation of actin cytoskeleton)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Graft-versus-host disease (Graft-versus-host disease)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Phosphatidylinositol signalling system (Phosphatidylinositol signalling system)	pathway		We found 17 significantly enriched pathways for depression	Positive
MDD	syndrome	Long-term depression (Long-term depression)	pathway		We found 17 significantly enriched pathways for depression	Positive