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Genetic correlates of insight in schizophrenia.

Publication ,  Journal Article
Xavier, RM; Vorderstrasse, A; Keefe, RSE; Dungan, JR
Published in: Schizophr Res
May 2018

UNLABELLED: Insight in schizophrenia is clinically important as it is associated with several adverse outcomes. Genetic contributions to insight are unknown. We examined genetic contributions to insight by investigating if polygenic risk scores (PRS) and candidate regions were associated with insight. METHOD: Schizophrenia case-only analysis of the Clinical Antipsychotics Trials of Intervention Effectiveness trial. Schizophrenia PRS was constructed using Psychiatric Genomics Consortium (PGC) leave-one out GWAS as discovery data set. For candidate regions, we selected 105 schizophrenia-associated autosomal loci and 11 schizophrenia-related oligodendrocyte genes. We used regressions to examine PRS associations and set-based testing for candidate analysis. RESULTS: We examined data from 730 subjects. Best-fit PRS at p-threshold of 1e-07 was associated with total insight (R2=0.005, P=0.05, empirical P=0.054) and treatment insight (R2=0.005, P=0.048, empirical P=0.048). For models that controlled for neurocognition, PRS significantly predicted treatment insight but at higher p-thresholds (0.1 to 0.5) but did not survive correction. Patients with highest polygenic burden had 5.9 times increased risk for poor insight compared to patients with lowest burden. PRS explained 3.2% (P=0.002, empirical P=0.011) of variance in poor insight. Set-based analyses identified two variants associated with poor insight- rs320703, an intergenic variant (within-set P=6e-04, FDR P=0.046) and rs1479165 in SOX2-OT (within-set P=9e-04, FDR P=0.046). CONCLUSION: To the best of our knowledge, this is the first study examining genetic basis of insight. We provide evidence for genetic contributions to impaired insight. Relevance of findings and necessity for replication are discussed.

Duke Scholars

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Published In

Schizophr Res

DOI

EISSN

1573-2509

Publication Date

May 2018

Volume

195

Start / End Page

290 / 297

Location

Netherlands

Related Subject Headings

  • Schizophrenia
  • SOXB1 Transcription Factors
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease
 

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Xavier, R. M., Vorderstrasse, A., Keefe, R. S. E., & Dungan, J. R. (2018). Genetic correlates of insight in schizophrenia. Schizophr Res, 195, 290–297. https://doi.org/10.1016/j.schres.2017.10.021
Xavier, Rose Mary, Allison Vorderstrasse, Richard S. E. Keefe, and Jennifer R. Dungan. “Genetic correlates of insight in schizophrenia.Schizophr Res 195 (May 2018): 290–97. https://doi.org/10.1016/j.schres.2017.10.021.
Xavier RM, Vorderstrasse A, Keefe RSE, Dungan JR. Genetic correlates of insight in schizophrenia. Schizophr Res. 2018 May;195:290–7.
Xavier, Rose Mary, et al. “Genetic correlates of insight in schizophrenia.Schizophr Res, vol. 195, May 2018, pp. 290–97. Pubmed, doi:10.1016/j.schres.2017.10.021.
Xavier RM, Vorderstrasse A, Keefe RSE, Dungan JR. Genetic correlates of insight in schizophrenia. Schizophr Res. 2018 May;195:290–297.
Journal cover image

Published In

Schizophr Res

DOI

EISSN

1573-2509

Publication Date

May 2018

Volume

195

Start / End Page

290 / 297

Location

Netherlands

Related Subject Headings

  • Schizophrenia
  • SOXB1 Transcription Factors
  • Psychiatry
  • Polymorphism, Single Nucleotide
  • Middle Aged
  • Male
  • Humans
  • Genotype
  • Genome-Wide Association Study
  • Genetic Predisposition to Disease