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

Hagg, 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., Sillanpaa, 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., 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, V. and Pedersen, N. L. (2017) Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. Translational Psychiatry, 7 4: 983-992. doi:10.1038/tp.2017.73


Author Hagg, 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.
Sillanpaa, 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.
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, V.
Pedersen, N. L.
Title Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
Journal name Translational Psychiatry   Check publisher's open access policy
ISSN 2158-3188
Publication date 2017-04-18
Year available 2014
Sub-type Article (original research)
DOI 10.1038/tp.2017.73
Open Access Status DOI
Volume 7
Issue 4
Start page 983
End page 992
Total pages 6
Place of publication London, United Kingdom
Publisher Nature Publishing Group
Language eng
Subject 2738 Psychiatry and Mental health
2804 Cellular and Molecular Neuroscience
2803 Biological Psychiatry
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.
Formatted 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 ε4 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 ε4-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 ε4-carriers might be at differential risk.
Keyword Respiratory System
Respiratory System
RESPIRATORY SYSTEM
Q-Index Code C1
Q-Index Status Provisional Code
Grant ID MR/K014536/1
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: HERDC Pre-Audit
Queensland Brain Institute Publications
Centre for Advanced Imaging Publications
 
Versions
Version Filter Type
Citation counts: TR Web of Science Citation Count  Cited 2 times in Thomson Reuters Web of Science Article | Citations
Scopus Citation Count Cited 3 times in Scopus Article | Citations
Google Scholar Search Google Scholar
Created: Mon, 19 Jun 2017, 01:00:46 EST by Web Cron on behalf of Learning and Research Services (UQ Library)