Please use this identifier to cite or link to this item: http://hdl.handle.net/2381/40170
Title: Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
Authors: Hägg, S.
Zhan, Y.
Karlsson, R.
Gerritsen, L.
Ploner, A.
van der Lee, S. J.
Broer, L.
Deelen, J.
Marioni, R. E.
Wong, A.
Lundquist, A.
Zhu, G.
Hansell, N. K.
Sillanpää, E.
Fedko, I. O.
Amin, N. A.
Beekman, M.
de Craen, A. J. M.
Degerman, S.
Harris, S. E.
Kan, K.-J.
Martin-Ruiz, C. M.
Montgomery, G. W.
NeuroCHARGE Cognitive Working Group
Adolfsson, A. N.
Reynolds, C. A.
Samani, N. J.
Suchiman, H. E. D.
Viljanen, A.
von Zglinicki, T.
Wright, M. J.
Hottenga, J.-J.
Boomsma, D. I.
Rantanen, T.
Kaprio, J. A.
Nyholt, D. R.
Martin, N. G.
Nyberg, L.
Adolfsson, R.
Kuh, D.
Starr, J. M.
Deary, I. J.
Slagboom, P. E.
van Duijn, C. M.
Codd, Veryan
Pedersen, N. L.
First Published: 18-Apr-2017
Publisher: Nature Publishing Group
Citation: Translational Psychiatry, 2017, 7 (4), e1100
Abstract: The association between telomere length (TL) dynamics on cognitive performance over the life-course is not well understood. This study meta-analyses observational and causal associations between TL and six cognitive traits, with stratifications on APOE genotype, in a Mendelian Randomization (MR) framework. Twelve European cohorts (N=17 052; mean age=59.2±8.8 years) provided results for associations between qPCR-measured TL (T/S-ratio scale) and general cognitive function, mini-mental state exam (MMSE), processing speed by digit symbol substitution test (DSST), visuospatial functioning, memory and executive functioning (STROOP). In addition, a genetic risk score (GRS) for TL including seven known genetic variants for TL was calculated, and used in associations with cognitive traits as outcomes in all cohorts. Observational analyses showed that longer telomeres were associated with better scores on DSST (β=0.051 per s.d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P=0.0002), and MMSE (β=0.025; 95% CI: 0.002, 0.047; P=0.03), and faster STROOP (β=-0.053; 95% CI: -0.087, -0.018; P=0.003). Effects for DSST were stronger in APOE ɛ4 non-carriers (β=0.081; 95% CI: 0.045, 0.117; P=1.0 × 10(-5)), whereas carriers performed better in STROOP (β=-0.074; 95% CI: -0.140, -0.009; P=0.03). Causal associations were found for STROOP only (β=-0.598 per s.d.-increase of TL; 95% CI: -1.125, -0.072; P=0.026), with a larger effect in ɛ4-carriers (β=-0.699; 95% CI: -1.330, -0.069; P=0.03). Two-sample replication analyses using CHARGE summary statistics showed causal effects between TL and general cognitive function and DSST, but not with STROOP. In conclusion, we suggest causal effects from longer TL on better cognitive performance, where APOE ɛ4-carriers might be at differential risk.
DOI Link: 10.1038/tp.2017.73
eISSN: 2158-3188
Links: http://www.nature.com/tp/journal/v7/n4/full/tp201773a.html
http://hdl.handle.net/2381/40170
Version: Publisher Version
Status: Peer-reviewed
Type: Journal Article
Rights: Copyright © the authors, 2017. This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Appears in Collections:Published Articles, Dept. of Cardiovascular Sciences

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