학술논문
A genome-wide association study of the longitudinal course of executive functions
Document Type
article
Author
Bernadette Wendel; Sergi Papiol; Till F. M. Andlauer; Jörg Zimmermann; Jens Wiltfang; Carsten Spitzer; Fanny Senner; Eva C. Schulte; Max Schmauß; Sabrina K. Schaupp; Jonathan Repple; Eva Reininghaus; Jens Reimer; Daniela Reich-Erkelenz; Nils Opel; Igor Nenadić; Susanne Meinert; Carsten Konrad; Farahnaz Klöhn-Saghatolislam; Tilo Kircher; Janos L. Kalman; Georg Juckel; Andreas Jansen; Markus Jäger; Maria Heilbronner; Martin von Hagen; Katrin Gade; Christian Figge; Andreas J. Fallgatter; Detlef E. Dietrich; Udo Dannlowski; Ashley L. Comes; Monika Budde; Bernhard T. Baune; Volker Arolt; Ion-George Anghelescu; Heike Anderson-Schmidt; Kristina Adorjan; Peter Falkai; Thomas G. Schulze; Heike Bickeböller; Urs Heilbronner
Source
Translational Psychiatry, Vol 11, Iss 1, Pp 1-8 (2021)
Subject
Language
English
ISSN
2158-3188
Abstract
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 = 7.2 × 10−10 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.