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

• Published in: Translational psychiatry Vol. 7; no. 4; p. e1100
• Main 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, 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
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 2017; Nature Publishing Group
• Subjects: 45/77; 692/53/2423; 706/648; Adult; Aged; Apolipoprotein E4 - genetics; Behavioral Sciences; Biological Psychology; Cognitive Dysfunction - diagnosis; Cognitive Dysfunction - genetics; Cohort Studies; Female; Genetic Carrier Screening; Genotype; Humans; Male; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Mendelian Randomization Analysis; Middle Aged; Neuropsychological Tests - statistics & numerical data; Neurosciences; Original; original-article; Pharmacotherapy; Psychiatry; Psychometrics; Statistics as Topic; Telomere - genetics; Whites - genetics
• ISSN: 2158-3188; 2158-3188
• DOI: 10.1038/tp.2017.73

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.