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.
Original language | English |
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Article number | e1100 |
Number of pages | 6 |
Journal | Translational Psychiatry |
Volume | 7 |
Issue number | 4 |
DOIs | |
Publication status | Published - 6 Mar 2017 |
Externally published | Yes |
Keywords
- apolipoprotein E4
- acyp2 gene
- adult
- ancestry group
- article
- cognition
- cognitive defect
- cohort analysis
- depth perception
- digit symbol substitution test
- episodic memory
- executive function
- female
- gene
- genetic association
- genetic risk
- genetic variability
- genome-wide association study
- genotype
- human
- learning
- major clinical study
- male
- Mendelian randomization analysis
- Mini Mental State Examination
- naf1 gene
- Netherlands
- obfc1 gene
- observational study
- pleiotropy
- polymerase chain reaction
- quantitative analysis
- rtel1 gene
- single nucleotide polymorphism
- Stroop test
- telomere length
- terc gene
- tert gene
- znf208 gene