Genetic Analysis of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk and Unique Genomic Associations DOI Creative Commons
Cuihua Xia, Ney Alliey‐Rodriguez,

C.A. Tamminga

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 8, 2024

Abstract The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These cut across DSM diagnoses of schizophrenia, schizoaffective disorder and bipolar with psychosis. Two recently developed post hoc ancestry adjustment methods Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow PRS analysis samples. Applied to schizophrenia PRS, we found the Khera AAPRS method show superior portability comparable prediction accuracy as compared Ge method. three disorders had similar AAPRSs ancestries. In genomic Biotypes, 12 genes isoforms showed significant associations specific Transcriptome-Wide Association Study (TWAS) genetically regulated expression (GReX) adult brain fetal brain. TWAS inflation was addressed by inclusion genotype principal components association analyses. Seven these genes/isoforms satisfied Mendelian Randomization (MR) criteria putative causality, including four TMEM140 , ARTN C1orf115 CYREN transcripts ENSG00000272941, ENSG00000257176, ENSG00000287733. are enriched biological pathways Rearranged during Transfection (RET) signaling, Neural Cell Adhesion Molecule 1 (NCAM1) interactions, NCAM signaling neurite out-growth. suggest that pharmacological clinical trials investigations might benefit from analyzing separately.

Language: Английский

Genetic analysis of psychosis Biotypes: shared Ancestry-adjusted polygenic risk and unique genomic associations DOI
Cuihua Xia, Ney Alliey‐Rodriguez, Carol A. Tamminga

et al.

Molecular Psychiatry, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 21, 2024

Language: Английский

Citations

2
Genetic Analysis of Psychosis Biotypes: Shared Ancestry-Adjusted Polygenic Risk and Unique Genomic Associations DOI Creative Commons
Cuihua Xia, Ney Alliey‐Rodriguez,

C.A. Tamminga

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 8, 2024

Abstract The Bipolar-Schizophrenia Network for Intermediate Phenotypes (B-SNIP) created psychosis Biotypes based on neurobiological measurements in a multi-ancestry sample. These cut across DSM diagnoses of schizophrenia, schizoaffective disorder and bipolar with psychosis. Two recently developed post hoc ancestry adjustment methods Polygenic Risk Scores (PRSs) generate Ancestry-Adjusted PRSs (AAPRSs), which allow PRS analysis samples. Applied to schizophrenia PRS, we found the Khera AAPRS method show superior portability comparable prediction accuracy as compared Ge method. three disorders had similar AAPRSs ancestries. In genomic Biotypes, 12 genes isoforms showed significant associations specific Transcriptome-Wide Association Study (TWAS) genetically regulated expression (GReX) adult brain fetal brain. TWAS inflation was addressed by inclusion genotype principal components association analyses. Seven these genes/isoforms satisfied Mendelian Randomization (MR) criteria putative causality, including four TMEM140 , ARTN C1orf115 CYREN transcripts ENSG00000272941, ENSG00000257176, ENSG00000287733. are enriched biological pathways Rearranged during Transfection (RET) signaling, Neural Cell Adhesion Molecule 1 (NCAM1) interactions, NCAM signaling neurite out-growth. suggest that pharmacological clinical trials investigations might benefit from analyzing separately.

Language: Английский

Citations

0