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

Wendel, Bernadette; Papiol, Sergi; Andlauer, Till F. M.; Zimmermann, Joerg; 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; Meinert, Susanne; Konrad, Carsten; Kloehn-Saghatolislam, Farahnaz; Kircher, Tilo; Kalman, Janos L.; Juckel, Georg; Jansen, Andreas; Jaeger, Markus; Heilbronner, Maria; Hagen, Martin von; Gade, Katrin; Figge, Christian; Fallgatter, Andreas J.; Dietrich, Detlef E.; Dannlowski, Udo; Comes, Ashley L.; Budde, Monika; Baune, Bernhard T.; Arolt, Volker; Anghelescu, Ion-George; Anderson-Schmidt, Heike; Adorjan, Kristina; Falkai, Peter; Schulze, Thomas G.; Bickeboeller, Heike und Heilbronner, Urs (2021): A genome-wide association study of the longitudinal course of executive functions. In: Translational Psychiatry, Bd. 11, Nr. 1, 386

Abstract

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 P value = 7.2x10(-10) 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 (P 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.

• Dokumententyp: Zeitschriftenartikel
• Fakultät: Medizin
• Themengebiete: 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit
• ISSN: 2158-3188
• Sprache: Englisch