Associations of schizophrenia risk genes ZNF804A and CACNA1C with schizotypy and modulation of attention in healthy subjects

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Tina Meller - , University of Marburg, Center for Mind, Brain and Behavior (Author)
  • Simon Schmitt - , University of Marburg, Center for Mind, Brain and Behavior (Author)
  • Frederike Stein - , University of Marburg, Center for Mind, Brain and Behavior (Author)
  • Katharina Brosch - , University of Marburg, Center for Mind, Brain and Behavior (Author)
  • Johannes Mosebach - , University of Marburg (Author)
  • Dilara Yüksel - , University of Marburg, SRI International (Author)
  • Dario Zaremba - , University of Münster (Author)
  • Dominik Grotegerd - , University of Münster (Author)
  • Katharina Dohm - , University of Münster (Author)
  • Susanne Meinert - , University of Münster (Author)
  • Katharina Förster - , University of Münster (Author)
  • Ronny Redlich - , University of Münster (Author)
  • Nils Opel - , University of Münster (Author)
  • Jonathan Repple - , University of Münster (Author)
  • Tim Hahn - , University of Münster (Author)
  • Andreas Jansen - , University of Marburg, Center for Mind, Brain and Behavior (Author)
  • Till F.M. Andlauer - , Max Planck Institute of Psychiatry, Technical University of Munich (Author)
  • Andreas J. Forstner - , University of Bonn, University of Marburg, University of Basel (Author)
  • Stefanie Heilmann-Heimbach - , University of Bonn (Author)
  • Fabian Streit - , Central Institute of Mental Health (CIMH) (Author)
  • Stephanie H. Witt - , Central Institute of Mental Health (CIMH) (Author)
  • Marcella Rietschel - , Central Institute of Mental Health (CIMH) (Author)
  • Bertram Müller-Myhsok - , Max Planck Institute of Psychiatry, Ludwig Maximilian University of Munich, University of Liverpool (UOL) (Author)
  • Markus M. Nöthen - , University of Bonn (Author)
  • Udo Dannlowski - , University of Münster (Author)
  • Axel Krug - , University of Marburg, Center for Mind, Brain and Behavior (Author)
  • Tilo Kircher - , University of Marburg, Center for Mind, Brain and Behavior (Author)
  • Igor Nenadić - , University of Marburg, Center for Mind, Brain and Behavior (Author)

Abstract

Schizotypy is a multidimensional risk phenotype distributed in the general population, constituting of subclinical, psychotic-like symptoms. It is associated with psychosis proneness, and several risk genes for psychosis are associated with schizotypy in non-clinical populations. Schizotypy might also modulate cognitive abilities as it is associated with attentional deficits in healthy subjects. In this study, we tested the hypothesis that established genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737 are associated with psychometric schizotypy and that schizotypy mediates their effect on attention or vice versa. In 615 healthy subjects from the FOR2107 cohort study, we analysed the genetic risk variants ZNF804A rs1344706 and CACNA1C rs1006737, psychometric schizotypy (schizotypal personality questionnaire-brief SPQ–B), and a neuropsychological measure of sustained and selective attention (d2 test). ZNF804A rs1344706 C (non-risk) alleles were significantly associated with higher SPQ-B Cognitive-Perceptual subscores in women and with attention deficits in both sexes. This schizotypy dimension also mediated the effect of ZNF804A on attention in women, but not in men. CACNA1C rs1006737-A showed a significant sex-modulated negative association with Interpersonal schizotypy only in men, and no effect on attention. Our multivariate model demonstrates differential genetic contributions of two psychosis risk genes to dimensions of schizotypy and, partly, to attention. This supports a model of shared genetic influence between schizotypy and cognitive functions impaired in schizophrenia.

Details

Original languageEnglish
Pages (from-to)67-75
Number of pages9
JournalSchizophrenia research
Volume208
Publication statusPublished - Jun 2019
Peer-reviewedYes
Externally publishedYes

External IDs

PubMed 31076262

Keywords

Sustainable Development Goals

Keywords

  • Attention, Cognition, Psychosis, Schizophrenia risk variants, Schizotypy

Library keywords