Differential GWAS of schizophrenia vs PTSD

Exploratory Score: 0.900 Price: $0.50 schizophrenia, post-traumatic stress disorder human patients - European ancestry and trans-ancestry populations Status: proposed

What This Experiment Tests

Exploratory experiment designed to discover new patterns targeting MAPT, CRHR1 in human patients - European ancestry and trans-ancestry populations. Primary outcome: differential genetic associations between SCZ and PTSD

Description

A differential genome-wide association study comparing the genetic architectures of schizophrenia (SCZ) and post-traumatic stress disorder (PTSD) using publicly available GWAS summary statistics from the Psychiatric Genomics Consortium (PGC). The study identified four independent loci with genome-wide significant differential associations between SCZ and PTSD in European ancestry individuals. These loci showed genome-wide significant associations with SCZ and nominal associations with PTSD but with opposite directions of effect. The analysis included trans-ancestry meta-analysis validation and focused particularly on the rs62062288 variant at the MAPT/CRHR1 locus on chromosome 17q21.31, which showed a risk effect for PTSD and protective effect for SCZ.

TARGET GENE
MAPT, CRHR1
MODEL SYSTEM
human patients - European ancestry and trans-ancestry populations
ESTIMATED COST
$0
TIMELINE
0 months
PATHWAY
neurodevelopmental pathways, stress response, tau protein regulation, corticotropin-releasing hormone signaling
SOURCE
extracted_from_pmid_41767305
PRIMARY OUTCOME
differential genetic associations between SCZ and PTSD

Scoring Dimensions

Info Gain 0.00 (25%) Feasibility 0.00 (20%) Hyp Coverage 0.00 (20%) Cost Effect. 0.00 (15%) Novelty 0.00 (10%) Ethical Safety 0.00 (10%) 0.900 composite

📖 Wiki Pages

MAPT — Microtubule Associated Protein Tau Gene EntgeneMAPT-Mutant NeuronscellCRHR1geneMAPT ProteinproteinMAPT - Microtubule-Associated Protein Tauscidex_docsMAPT→Tau→Aggregation→PSP Causal ChainmechanismMAPT Haplotypes (H1/H2)genePGC-1α Mitochondrial Biogenesis Comparison — AD/PDmechanismPGC-1α and Mitochondrial Biogenesis Therapies for therapeuticmapt-variantsdiseaseMAPT Mutation Penetrance and Phenotypic Modifiers gapPGC-1α ProteinproteinGWAS Findings HubmechanismGWAS Findings Hub: Alzheimer's and Parkinson's DismechanismPGC-1α (PPARGC1A)protein

Protocol

Differential GWAS analysis using PGC summary statistics, followed by trans-ancestry meta-analysis validation and GTEx expression quantitative trait locus (eQTL) analysis to examine regulatory effects on gene expression in brain tissues

Expected Outcomes

Identification of genetic loci with opposing effects on SCZ and PTSD risk, with validation of brain-region-specific regulatory effects on target genes

Success Criteria

genome-wide significance threshold P < 5 × 10^-8 for differential associations

Related Hypotheses (5)

Glymphatic-Mediated Tau Clearance Dysfunction0.781
Dual-Circuit Tau Vulnerability Cascade0.734
Dopaminergic Ventral Tegmental-Hippocampal Circuit Protection0.729
Cholinergic Basal Forebrain-Hippocampal Circuit Protection0.728
Locus Coeruleus-Hippocampal Circuit Protection0.637

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