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

Wendel, B., Papiol, S., Andlauer, T. F. M., Zimmermann, J., Wiltfang, J., Spitzer, C., et al. (2021). A genome-wide association study of the longitudinal course of executive functions. TRANSLATIONAL PSYCHIATRY, 11(1): 386. doi:10.1038/s41398-021-01510-8.

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Wendel, Bernadette, Author
Papiol, Sergi, Author
Andlauer, Till F. M., Author
Zimmermann, Joerg, Author
Wiltfang, Jens, Author
Spitzer, Carsten, Author
Senner, Fanny, Author
Schulte, Eva C., Author
Schmauss, Max, Author
Schaupp, Sabrina K., Author
Repple, Jonathan, Author
Reininghaus, Eva, Author
Reimer, Jens, Author
Reich-Erkelenz, Daniela, Author
Opel, Nils, Author
Meinert, Susanne, Author
Konrad, Carsten, Author
Kloehn-Saghatolislam, Farahnaz, Author
Kircher, Tilo, Author
Kalman, Janos L.1, Author           
Juckel, Georg, AuthorJansen, Andreas, AuthorJaeger, Markus, AuthorHeilbronner, Maria, Authorvon Hagen, Martin, AuthorGade, Katrin, AuthorFigge, Christian, AuthorFallgatter, Andreas J., AuthorDietrich, Detlef E., AuthorDannlowski, Udo, AuthorComes, Ashley L., AuthorBudde, Monika, AuthorBaune, Bernhard T., AuthorArolt, Volker, AuthorAnghelescu, Ion-George, AuthorAnderson-Schmidt, Heike, AuthorAdorjan, Kristina, AuthorFalkai, Peter, AuthorSchulze, Thomas G., AuthorBickeboeller, Heike, AuthorHeilbronner, Urs, Author more..
Affiliations:
1IMPRS Translational Psychiatry, Max Planck Institute of Psychiatry, Max Planck Society, ou_3318616              

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 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.

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 Dates: 2021
 Publication Status: Published online
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Title: TRANSLATIONAL PSYCHIATRY
Source Genre: Journal
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Pages: - Volume / Issue: 11 (1) Sequence Number: 386 Start / End Page: - Identifier: ISSN: 2158-3188