Association of genetic variants at 22q11.2 chromosomal region with cognitive performance in Japanese patients with schizophrenia

Kazufumi Akiyama, Atsushi Saito, Satoshi Saito, Yuji Ozeki, Takashi Watanabe, Kumiko Fujii, Kazutaka Shimoda

Research output: Contribution to journalArticle

Abstract

22q11.2 heterozygous multigene deletions confer an increased risk of schizophrenia with marked impairment of cognition. We explored whether genes on 22q11.2 are associated with cognitive performance in patients with idiopathic schizophrenia. A total of 240 schizophrenia patients and 240 healthy controls underwent the Japanese-language version of the Brief Assessment of Cognition in Schizophrenia (BACS)and were genotyped for 115 tag single-nucleotide polymorphisms (tag SNPs)at the 22q11.2 region using the golden gate assay (Illumina®). Associations between z-scores of the BACS cognitive domains and SNPs and haplotypes were analyzed using linear regression in PLINK 1.07. An additional set of 149 patients with bipolar disorder were included for cognitive assessment and selected SNPs were genotyped using real-time PCR. Patients with schizophrenia and bipolar disorder showed qualitatively comparable profiles of cognitive impairment across BACS subdomains, as revealed by significant correlation between the two groups in the resulting cognitive effect sizes relative to controls. rs4819522 (TBX1)and rs2238769 (UFD1L)were significantly and nominally associated, respectively, with symbol coding in patients with schizophrenia. Haplotype analyses revealed that haplotypes containing the A allele at rs4819522 and G allele at rs2238769 showed significant negative associations with symbol coding in patients with schizophrenia. There was no effect of any haplotypes on cognition in patients with bipolar disorder. Our results have implications for the understanding of the role of haplotypes of UFD1L and TBX1 genes associated with symbol coding in patients with schizophrenia. Further replication studies in a cohort of newly diagnosed patients and other ethnicities are warranted.

Original languageEnglish (US)
Article number100134
JournalSchizophrenia Research: Cognition
Volume17
DOIs
StatePublished - Sep 1 2019

Fingerprint

Schizophrenia
Cognition
Haplotypes
Bipolar Disorder
Single Nucleotide Polymorphism
Alleles
Genes
Real-Time Polymerase Chain Reaction
Linear Models
Language

Keywords

  • 22q11.2
  • BACS
  • Schizophrenia
  • Symbol coding
  • TBX1
  • UFD1L

ASJC Scopus subject areas

  • Cognitive Neuroscience
  • Psychiatry and Mental health

Cite this

Association of genetic variants at 22q11.2 chromosomal region with cognitive performance in Japanese patients with schizophrenia. / Akiyama, Kazufumi; Saito, Atsushi; Saito, Satoshi; Ozeki, Yuji; Watanabe, Takashi; Fujii, Kumiko; Shimoda, Kazutaka.

In: Schizophrenia Research: Cognition, Vol. 17, 100134, 01.09.2019.

Research output: Contribution to journalArticle

Akiyama, Kazufumi ; Saito, Atsushi ; Saito, Satoshi ; Ozeki, Yuji ; Watanabe, Takashi ; Fujii, Kumiko ; Shimoda, Kazutaka. / Association of genetic variants at 22q11.2 chromosomal region with cognitive performance in Japanese patients with schizophrenia. In: Schizophrenia Research: Cognition. 2019 ; Vol. 17.
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