A genome-wide association study of the longitudinal course of executive functions
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A genome-wide association study of the longitudinal course of executive functions. / 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; Heilbronner, Maria; von Hagen, Martin; 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; Bickeböller, Heike; Heilbronner, Urs.
in: TRANSL PSYCHIAT, Jahrgang 11, Nr. 1, 386, 10.07.2021.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - A genome-wide association study of the longitudinal course of executive functions
AU - Wendel, Bernadette
AU - Papiol, Sergi
AU - Andlauer, Till F M
AU - Zimmermann, Jörg
AU - Wiltfang, Jens
AU - Spitzer, Carsten
AU - Senner, Fanny
AU - Schulte, Eva C
AU - Schmauß, Max
AU - Schaupp, Sabrina K
AU - Repple, Jonathan
AU - Reininghaus, Eva
AU - Reimer, Jens
AU - Reich-Erkelenz, Daniela
AU - Opel, Nils
AU - Nenadić, Igor
AU - Meinert, Susanne
AU - Konrad, Carsten
AU - Klöhn-Saghatolislam, Farahnaz
AU - Kircher, Tilo
AU - Kalman, Janos L
AU - Juckel, Georg
AU - Jansen, Andreas
AU - Jäger, Markus
AU - Heilbronner, Maria
AU - von Hagen, Martin
AU - Gade, Katrin
AU - Figge, Christian
AU - Fallgatter, Andreas J
AU - Dietrich, Detlef E
AU - Dannlowski, Udo
AU - Comes, Ashley L
AU - Budde, Monika
AU - Baune, Bernhard T
AU - Arolt, Volker
AU - Anghelescu, Ion-George
AU - Anderson-Schmidt, Heike
AU - Adorjan, Kristina
AU - Falkai, Peter
AU - Schulze, Thomas G
AU - Bickeböller, Heike
AU - Heilbronner, Urs
N1 - © 2021. The Author(s).
PY - 2021/7/10
Y1 - 2021/7/10
N2 - 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.
AB - 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.
KW - Executive Function
KW - Genome-Wide Association Study
KW - Genotype
KW - Humans
KW - Linkage Disequilibrium
KW - Polymorphism, Single Nucleotide
U2 - 10.1038/s41398-021-01510-8
DO - 10.1038/s41398-021-01510-8
M3 - SCORING: Journal article
C2 - 34247186
VL - 11
JO - TRANSL PSYCHIAT
JF - TRANSL PSYCHIAT
SN - 2158-3188
IS - 1
M1 - 386
ER -
