Genome-wide gene pathway analysis of psychotic illness symptom dimensions based on a new schizophrenia-specific model of the OPCRIT

Schizophrenia Research
Anna R DochertyAyman H Fanous

Abstract

Empirically derived phenotypic measurements have the potential to enhance gene-finding efforts in schizophrenia. Previous research based on factor analyses of symptoms has typically included schizoaffective cases. Deriving factor loadings from analysis of only narrowly defined schizophrenia cases could yield more sensitive factor scores for gene pathway and gene ontology analyses. Using an Irish family sample, this study 1) factor analyzed clinician-rated Operational Criteria Checklist items in cases with schizophrenia only, 2) scored the full sample based on these factor loadings, and 3) implemented genome-wide association, gene-based, and gene-pathway analysis of these SCZ-based symptom factors (final N=507). Three factors emerged from the analysis of the schizophrenia cases: a manic, a depressive, and a positive symptom factor. In gene-based analyses of these factors, multiple genes had q<0.01. Of particular interest are findings for PTPRG and WBP1L, both of which were previously implicated by the Psychiatric Genomics Consortium study of SCZ; results from this study suggest that variants in these genes might also act as modifiers of SCZ symptoms. Gene pathway analyses of the first factor indicated over-representation of glut...Continue Reading

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Citations

Dec 27, 2015·Schizophrenia Research·Seong ShimErica Duncan
Sep 11, 2019·The Journal of Nervous and Mental Disease·Snežana UroševićScott R Sponheim
Dec 17, 2019·American Journal of Medical Genetics. Part B, Neuropsychiatric Genetics : the Official Publication of the International Society of Psychiatric Genetics·Fanglin GuanTianxiao Zhang
Oct 18, 2016·Molecular Medicine Reports·E RizosV Zoumpourlis
Jul 10, 2020·BMC Medical Genomics·Laith N Al-EitanFiras A Al-Qarqaz
Jan 4, 2017·Current Behavioral Neuroscience Reports·Anna R DochertyAyman H Fanous
May 23, 2018·Schizophrenia Bulletin·Anna R DochertyAlex S Cohen
Nov 18, 2017·Schizophrenia Research·Kirsten E S CraddockJudith L Rapoport
May 28, 2021·Frontiers in Psychiatry·Humberto NicoliniMaría Elena Medina-Mora
Sep 12, 2021·Seminars in Cell & Developmental Biology·Lena Palaniyappan

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