Polygenic pleiotropy and potential causal relationships between educational attainment, neurobiological profile, and positive psychotic symptoms

Translational Psychiatry
Yen-Feng LinMei-Hua Hall

Abstract

Event-related potential (ERP) components have been used to assess cognitive functions in patients with psychotic illness. Evidence suggests that among patients with psychosis there is a distinct heritable neurophysiologic phenotypic subtype captured by impairments across a range of ERP measures. In this study, we investigated the genetic basis of this "globally impaired" ERP cluster and its relationship to psychosis and cognitive abilities. We applied K-means clustering to six ERP measures to re-derive the globally impaired (n = 60) and the non-globally impaired ERP clusters (n = 323) in a sample of cases with schizophrenia (SCZ = 136) or bipolar disorder (BPD = 121) and healthy controls (n = 126). We used genome-wide association study (GWAS) results for SCZ, BPD, college completion, and childhood intelligence as the discovery datasets to derive polygenic risk scores (PRS) in our study sample and tested their associations with globally impaired ERP. We conducted mediation analyses to estimate the proportion of each PRS effect on severity of psychotic symptoms that is mediated through membership in the globally impaired ERP. Individuals with globally impaired ERP had significantly higher PANSS-positive scores (β = 3.95, P = 0.00...Continue Reading

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Citations

Mar 2, 2019·Journal of Aging and Health·Aniruddha Das
May 31, 2019·Journal of Aging and Health·Aniruddha Das
Nov 22, 2019·The Journals of Gerontology. Series B, Psychological Sciences and Social Sciences·Aniruddha Das
Jan 24, 2021·NPJ Schizophrenia·Adam SocratesPaul F O'Reilly

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IMPUTE2
PRSice
SHAPEIT
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EIGENSTRAT
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STATA
POLYGENESCORE
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