Short telomere length is associated with impaired cognitive performance in European ancestry cohorts

S. Hägg, Y Zhan, R. Karlsson, L. Gerritsen, A. Ploner, J.-S. Lee, L. Broer, J. Deelen, Riccardo E Marioni, A Wong, A Lundquist, G. Zhu, Narelle K Hansell, E. Sillanpää, I O Fedko, N A Amin, M Beekman, A.J.M. Craen, S Degerman, S E HarrisK-J Kan, C. Martin-Ruiz, Grant W Montgomery, A N Adolfsson, C.A. Reynolds, Nilesh J Samani, H E D Suchiman, A Viljanen, T von Zglinicki, Margaret J Wright, J-J Hottenga, D I Boomsma, T. Rantanen, J A Kaprio, D R Nyholt, Nicholas G Martin, L. Nyberg, R Adolfsson, D Kuh, J. M. Starr, I. J. Deary, P. Eline Slagboom, Cornelia M van Duijn, V. Codd, Nancy L Pedersen, NeuroCHARGE Cognitive Working Group

Research output: Contribution to JournalArticleAcademicpeer-review


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.

Original languageEnglish
Article numbere1100
Pages (from-to)e1100
JournalTranslational Psychiatry
Issue number4
Publication statusPublished - 18 Apr 2017


European Network for Genetic and Genomic Epidemiology (ENGAGE) with FP7-HEALTH-F4-2007 grant agreement nr. 201413. The Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium (CHARGE) which is supported in part by the National Heart, Lung and Blood Institute grant HL105756 and the neuroCHARGE cognitive working group through the National Institute on Aging grant AG033193. All cohort-specific acknowledgments are found in the Supplementary Data.

FundersFunder number
Cohorts for Heart and Aging Research in Genomic
National Institute on AgingR01AG033193
National Heart, Lung, and Blood InstituteHL105756


    • Journal Article

    Cohort Studies

    • Netherlands Twin Register (NTR)


    Dive into the research topics of 'Short telomere length is associated with impaired cognitive performance in European ancestry cohorts'. Together they form a unique fingerprint.

    Cite this