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

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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 , NeuroCHARGE Cognitive Working Grp & ENGAGE Consortium 2017 , ' Short telomere length is associated with impaired cognitive performance in European ancestry cohorts ' , Translational Psychiatry , vol. 7 , 1100 . https://doi.org/10.1038/tp.2017.73

Title: Short telomere length is associated with impaired cognitive performance in European ancestry cohorts
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.; NeuroCHARGE Cognitive Working Grp; ENGAGE Consortium
Contributor: University of Helsinki, Clinicum
Date: 2017-04-18
Language: eng
Number of pages: 6
Belongs to series: Translational Psychiatry
ISSN: 2158-3188
URI: http://hdl.handle.net/10138/199197
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-measuredTL (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 (beta = 0.051 per s. d.-increase of TL; 95% confidence interval (CI): 0.024, 0.077; P = 0.0002), and MMSE (beta = 0.025; 95% CI: 0.002, 0.047; P = 0.03), and faster STROOP (beta = -0.053; 95% CI: -0.087, -0.018; P = 0.003). Effects for DSST were stronger in APOE epsilon 4 non-carriers (beta = 0.081; 95% CI: 0.045, 0.117; P = 1.0 x 10(-5)), whereas carriers performed better in STROOP (beta = -0.074; 95% CI: -0.140, -0.009; P = 0.03). Causal associations were found for STROOP only (beta = -0.598 per s. d.-increase of TL; 95% CI: -1.125, -0.072; P = 0.026), with a larger effect in epsilon 4-carriers (beta = -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 epsilon 4-carriers might be at differential risk.
Subject: MENDELIAN RANDOMIZATION
PROCESSING SPEED
YOUNG-ADULTS
DISEASE
MORTALITY
DEMENTIA
RISK
GWAS
IDENTIFICATION
METAANALYSIS
3124 Neurology and psychiatry
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