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Short telomere length is associated with impaired cognitive performance in European ancestry cohorts.
Tuesday,2018-01-16 18:15 America/Los_Angeles — ecterry
| Title | Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. |
| Publication Type | Journal Article |
| Year of Publication | 2017 |
| Authors | Hägg, S, Zhan, Y, Karlsson, R, Gerritsen, L, Ploner, A, van der Lee, SJ, Broer, L, Deelen, J, Marioni, RE, Wong, A, Lundquist, A, Zhu, G, Hansell, NK, Sillanpää, E, Fedko, IO, Amin, NA, Beekman, M, de Craen, AJM, Degerman, S, Harris, SE, Kan, K-J, Martin-Ruiz, CM, Montgomery, GW, Adolfsson, AN, Reynolds, CA, Samani, NJ, Suchiman, HED, Viljanen, A, von Zglinicki, T, Wright, MJ, Hottenga, J-J, Boomsma, DI, Rantanen, T, Kaprio, JA, Nyholt, DR, Martin, NG, Nyberg, L, Adolfsson, R, Kuh, D, Starr, JM, Deary, IJ, Slagboom, PE, van Duijn, CM, Codd, V, Pedersen, NL |
| Corporate/Institutional Authors | NeuroCHARGE Cognitive Working Group |
| Journal | Transl Psychiatry |
| Volume | 7 |
| Issue | 4 |
| Pagination | e1100 |
| Date Published | 2017 04 18 |
| ISSN | 2158-3188 |
| Keywords | Adult, Aged, Apolipoprotein E4, Cognitive Dysfunction, Cohort Studies, European Continental Ancestry Group, Female, Genetic Carrier Screening, Genotype, Humans, Male, Mendelian Randomization Analysis, Middle Aged, Neuropsychological Tests, Psychometrics, Statistics as Topic, Telomere |
| Abstract | <p>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.</p> |
| DOI | 10.1038/tp.2017.73 |
| Alternate Journal | Transl Psychiatry |
| PubMed ID | 28418400 |
| PubMed Central ID | PMC5416710 |
| Grant List | R01 AG033193 / AG / NIA NIH HHS / United States R01 HL105756 / HL / NHLBI NIH HHS / United States |
ePub date:
17/04