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Wendel, Bernadette; Papiol, Sergi; Andlauer, Till F. M.; Zimmermann, Jörg; Wiltfang, Jens; Spitzer, Carsten; Senner, Fanny; Schulte, Eva C.; Schmauß, Max; Schaupp, Sabrina K.; Repple, Jonathan; Reininghaus, Eva; Reimer, Jens; Reich-Erkelenz, Daniela; Opel, Nils; Nenadić, Igor; Meinert, Susanne; Konrad, Carsten; Klöhn-Saghatolislam, Farahnaz; Kircher, Tilo; Kalman, Janos L.; Juckel, Georg; Jansen, Andreas; Jäger, Markus; [...]

A genome-wide association study of the longitudinal course of executive functions

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  • Medientyp: E-Artikel
  • Titel: A genome-wide association study of the longitudinal course of executive functions
  • Beteiligte: Wendel, Bernadette; Papiol, Sergi; Andlauer, Till F. M.; Zimmermann, Jörg; Wiltfang, Jens; Spitzer, Carsten; Senner, Fanny; Schulte, Eva C.; Schmauß, Max; Schaupp, Sabrina K.; Repple, Jonathan; Reininghaus, Eva; Reimer, Jens; Reich-Erkelenz, Daniela; Opel, Nils; Nenadić, Igor; Meinert, Susanne; Konrad, Carsten; Klöhn-Saghatolislam, Farahnaz; Kircher, Tilo; Kalman, Janos L.; Juckel, Georg; Jansen, Andreas; Jäger, Markus; [...]
  • Erschienen: Springer Science and Business Media LLC, 2021
  • Erschienen in: Translational Psychiatry
  • Sprache: Englisch
  • DOI: 10.1038/s41398-021-01510-8
  • ISSN: 2158-3188
  • Schlagwörter: Biological Psychiatry ; Cellular and Molecular Neuroscience ; Psychiatry and Mental health
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  • Beschreibung: <jats:title>Abstract</jats:title><jats:p>Executive functions are metacognitive capabilities that control and coordinate mental processes. In the transdiagnostic PsyCourse Study, comprising patients of the affective-to-psychotic spectrum and controls, we investigated the genetic basis of the time course of two core executive subfunctions: set-shifting (Trail Making Test, part B (TMT-B)) and updating (Verbal Digit Span backwards) in 1338 genotyped individuals. Time course was assessed with four measurement points, each 6 months apart. Compared to the initial assessment, executive performance improved across diagnostic groups. We performed a genome-wide association study to identify single nucleotide polymorphisms (SNPs) associated with performance change over time by testing for SNP-by-time interactions using linear mixed models. We identified nine genome-wide significant SNPs for TMT-B in strong linkage disequilibrium with each other on chromosome 5. These were associated with decreased performance on the continuous TMT-B score across time. Variant rs150547358 had the lowest <jats:italic>P</jats:italic> value = 7.2 × 10<jats:sup>−10</jats:sup> with effect estimate beta = 1.16 (95% c.i.: 1.11, 1.22). Implementing data of the FOR2107 consortium (1795 individuals), we replicated these findings for the SNP rs150547358 (<jats:italic>P</jats:italic> value = 0.015), analyzing the difference of the two available measurement points two years apart. In the replication study, rs150547358 exhibited a similar effect estimate beta = 0.85 (95% c.i.: 0.74, 0.97). Our study demonstrates that longitudinally measured phenotypes have the potential to unmask novel associations, adding time as a dimension to the effects of genomics.</jats:p>
  • Zugangsstatus: Freier Zugang