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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-04-18

AUTHORS

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

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. More... »

PAGES

e1100

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/tp.2017.73

DOI

http://dx.doi.org/10.1038/tp.2017.73

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1084920379

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28418400


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