SynthesisBiological psychiatry2025
Dissecting Schizophrenia Biology Using Pleiotropy With Cognitive Genomics.
Synthesis in Biological psychiatry, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Disorder-specific and shared genetic architecture underlying schizophrenia and bipolar disorder.medRxiv : the preprint server for health sciences · 2026Article
- Polygenic risk score for neurodevelopmental disorders and cognitive impairment at long-term follow-up of first-episode psychosis.European archives of psychiatry and clinical neuroscience · 2026Article
- Cognitive pleiotropy reveals disorder-specific and shared biology for schizophrenia and bipolar disorder.medRxiv : the preprint server for health sciences · 2026Article
- Allele-Specific Methylation Links Non-coding Variant of rs2280906 to MYOM2 Regulation in Schizophrenia.Molecular neurobiology · 2025Article
- Pleiotropy in Multitrait Genome-Wide Association Studies: Approaches and Insights From Schizophrenia-Cognition Analyses.Biological psychiatry · 2025Article
- Inflammatory and Oxidative Biological Profiles in Mental Disorders: Perspectives on Diagnostics and Personalized Therapy.International journal of molecular sciences · 2025Review
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Abstract
backgroundGiven the increasingly large number of loci discovered by psychiatric genome-wide association studies (GWASs), specification of the key biological pathways that underlie these loci has become a priority for the field. We have previously leveraged the pleiotropic genetic relationships between schizophrenia (SCZ) and 2 cognitive phenotypes (educational attainment and cognitive task performance) to differentiate 2 subsets of illness-relevant single nucleotide polymorphisms (SNPs): 1) those with concordant alleles, which are associated with reduced cognitive performance and educational attainment and increased SCZ risk, and 2) those with discordant alleles, which are linked to reduced educational and/or cognitive levels but lower SCZ susceptibility.
methodsIn the current study, we extended our prior work, utilizing larger input GWAS datasets and a more powerful statistical approach to pleiotropic meta-analysis, the pleiotropic locus exploration and interpretation using optimal test (PLEIO).
resultsOur pleiotropic meta-analysis of SCZ and the 2 cognitive phenotypes revealed 768 significant pleiotropic loci (166 novel). Among these, 347 loci harbored concordant SNPs, 270 encompassed discordant SNPs, and 151 dual loci contained concordant and discordant SNPs. Competitive gene-set analysis using MAGMA linked concordant SNP loci with neurodevelopmental pathways (e.g., neurogenesis), whereas discordant loci were associated with mature neuronal synaptic functions. These distinctions were also observed in BrainSpan analysis of temporal enrichment patterns across developmental periods, with concordant loci containing more prenatally expressed genes than discordant loci. Dual loci were enriched for genes related to messenger RNA translation initiation, which represents a novel finding in the SCZ literature.
conclusionsPleiotropic analysis permits not only enhanced statistical power for locus discovery but also the ability to parse distinct biological processes associated with endophenotypes.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.