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Wendel, B; Papiol, S; Andlauer, TFM; Zimmermann, J; Wiltfang, J; Spitzer, C; Senner, F; Schulte, EC; Schmauß, M; Schaupp, SK; Repple, J; Reininghaus, E; Reimer, J; Reich-Erkelenz, D; Opel, N; Nenadić, I; Meinert, S; Konrad, C; Klöhn-Saghatolislam, F; Kircher, T; Kalman, JL; Juckel, G; Jansen, A; Jäger, M; Heilbronner, M; von, Hagen, M; Gade, K; Figge, C; Fallgatter, AJ; Dietrich, DE; Dannlowski, U; Comes, AL; Budde, M; Baune, BT; Arolt, V; Anghelescu, IG; Anderson-Schmidt, H; Adorjan, K; Falkai, P; Schulze, TG; Bickeböller, H; Heilbronner, U.
A genome-wide association study of the longitudinal course of executive functions.
Transl Psychiatry. 2021; 11(1): 386 Doi: 10.1038/s41398-021-01510-8 [OPEN ACCESS]
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Reininghaus Eva

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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.
Find related publications in this database (using NLM MeSH Indexing)
Executive Function - administration & dosage
Genome-Wide Association Study - administration & dosage
Genotype - administration & dosage
Humans - administration & dosage
Linkage Disequilibrium - administration & dosage
Polymorphism, Single Nucleotide - administration & dosage

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