Back to Search
Start Over
Pathway-based polygene risk for severe depression implicates drug metabolism in CONVERGE
- Source :
- Psychol Med
- Publication Year :
- 2019
-
Abstract
- BackgroundThe Psychiatric Genomics Consortium (PGC) has made major advances in the molecular etiology of MDD, confirming that MDD is highly polygenic. Pathway enrichment results from PGC meta-analyses can also be used to help inform molecular drug targets. Prior to any knowledge of molecular biomarkers for MDD, drugs targeting molecular pathways (MPs) proved successful in treating MDD. It is possible that examining polygenicity within specific MPs implicated in MDD can further refine molecular drug targets.MethodsUsing a large case–control GWAS based on low-coverage whole genome sequencing (N = 10 640) in Han Chinese women, we derived polygenic risk scores (PRS) for MDD and for MDD specific to each of over 300 MPs previously shown to be relevant to psychiatric diagnoses. We then identified sets of PRSs, accounting for critical covariates, significantly predictive of case status.ResultsOver and above global MDD polygenic risk, polygenic risk within the GO: 0017144 drug metabolism pathway significantly predicted recurrent depression after multiple testing correction. Secondary transcriptomic analysis suggests that among genes in this pathway, CYP2C19 (family of Cytochrome P450) and CBR1 (Carbonyl Reductase 1) might be most relevant to MDD. Within the cases, pathway-based risk was additionally associated with age at onset of MDD.ConclusionsResults indicate that pathway-based risk might inform etiology of recurrent major depression. Future research should examine whether polygenicity of the drug metabolism gene pathway has any association with clinical presentation or treatment response. We discuss limitations to the generalizability of these preliminary findings, and urge replication in future research.
- Subjects :
- Drug
Adult
China
Multifactorial Inheritance
media_common.quotation_subject
Genome-wide association study
Genomics
CYP2C19
Bioinformatics
behavioral disciplines and activities
Polymorphism, Single Nucleotide
Article
Transcriptome
03 medical and health sciences
0302 clinical medicine
Asian People
Recurrence
Risk Factors
mental disorders
Medicine
Humans
Genetic Predisposition to Disease
Age of Onset
Applied Psychology
Depression (differential diagnoses)
030304 developmental biology
media_common
0303 health sciences
Depressive Disorder, Major
business.industry
Middle Aged
Psychiatry and Mental health
Polygene
Case-Control Studies
Etiology
Female
business
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- ISSN :
- 14698978 and 00332917
- Volume :
- 50
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- Psychological medicine
- Accession number :
- edsair.doi.dedup.....f101f93af09472cad36b3758e60b40dd