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

S. Hägg, Y Zhan, R. Karlsson, L. Gerritsen, A. Ploner, J.-S. Lee, L. Broer, J. Deelen, Riccardo E Marioni, A Wong, A Lundquist, G. Zhu, Narelle K Hansell, E. Sillanpää, I O Fedko, N A Amin, M Beekman, A.J.M. Craen, S Degerman, S E Harris & 26 others K-J Kan, C. Martin-Ruiz, Grant W Montgomery, A N Adolfsson, C.A. Reynolds, Nilesh J Samani, H E D Suchiman, A Viljanen, T von Zglinicki, Margaret J Wright, J-J Hottenga, D I Boomsma, T. Rantanen, J A Kaprio, D R Nyholt, Nicholas G Martin, L. Nyberg, R Adolfsson, D Kuh, J. M. Starr, I. J. Deary, P. Eline Slagboom, Cornelia M van Duijn, V. Codd, Nancy L Pedersen, NeuroCHARGE Cognitive Working Group

Research output: Contribution to JournalArticleAcademicpeer-review

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.

Original languageEnglish
Pages (from-to)e1100
JournalTranslational Psychiatry
Volume7
Issue number4
DOIs
Publication statusPublished - 18 Apr 2017

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Telomere
Confidence Intervals
Cognition
Random Allocation
Meta-Analysis
Genotype

Keywords

  • Journal Article

Cite this

Hägg, S., Zhan, Y., Karlsson, R., Gerritsen, L., Ploner, A., Lee, J-S., ... NeuroCHARGE Cognitive Working Group (2017). Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. Translational Psychiatry, 7(4), e1100. https://doi.org/10.1038/tp.2017.73
Hägg, S. ; Zhan, Y ; Karlsson, R. ; Gerritsen, L. ; Ploner, A. ; Lee, J.-S. ; Broer, L. ; Deelen, J. ; Marioni, Riccardo E ; Wong, A ; Lundquist, A ; Zhu, G. ; Hansell, Narelle K ; Sillanpää, E. ; Fedko, I O ; Amin, N A ; Beekman, M ; Craen, A.J.M. ; Degerman, S ; Harris, S E ; Kan, K-J ; Martin-Ruiz, C. ; Montgomery, Grant W ; Adolfsson, A N ; Reynolds, C.A. ; Samani, Nilesh J ; Suchiman, H E D ; Viljanen, A ; von Zglinicki, T ; Wright, Margaret J ; Hottenga, J-J ; Boomsma, D I ; Rantanen, T. ; Kaprio, J A ; Nyholt, D R ; Martin, Nicholas G ; Nyberg, L. ; Adolfsson, R ; Kuh, D ; Starr, J. M. ; Deary, I. J. ; Slagboom, P. Eline ; van Duijn, Cornelia M ; Codd, V. ; Pedersen, Nancy L ; NeuroCHARGE Cognitive Working Group. / Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. In: Translational Psychiatry. 2017 ; Vol. 7, No. 4. pp. e1100.
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title = "Short telomere length is associated with impaired cognitive performance in European ancestry cohorts",
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.",
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Hägg, S, Zhan, Y, Karlsson, R, Gerritsen, L, Ploner, A, Lee, J-S, Broer, L, Deelen, J, Marioni, RE, Wong, A, Lundquist, A, Zhu, G, Hansell, NK, Sillanpää, E, Fedko, IO, Amin, NA, Beekman, M, Craen, AJM, Degerman, S, Harris, SE, Kan, K-J, Martin-Ruiz, C, 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 & NeuroCHARGE Cognitive Working Group 2017, 'Short telomere length is associated with impaired cognitive performance in European ancestry cohorts' Translational Psychiatry, vol. 7, no. 4, pp. e1100. https://doi.org/10.1038/tp.2017.73

Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. / Hägg, S.; Zhan, Y; Karlsson, R.; Gerritsen, L.; Ploner, A.; Lee, J.-S.; Broer, L.; Deelen, J.; Marioni, Riccardo E; Wong, A; Lundquist, A; Zhu, G.; Hansell, Narelle K; Sillanpää, E.; Fedko, I O; Amin, N A; Beekman, M; Craen, A.J.M.; Degerman, S; Harris, S E; Kan, K-J; Martin-Ruiz, C.; Montgomery, Grant W; Adolfsson, A N; Reynolds, C.A.; Samani, Nilesh J; Suchiman, H E D; Viljanen, A; von Zglinicki, T; Wright, Margaret J; Hottenga, J-J; Boomsma, D I; Rantanen, T.; Kaprio, J A; Nyholt, D R; Martin, Nicholas G; Nyberg, L.; Adolfsson, R; Kuh, D; Starr, J. M.; Deary, I. J.; Slagboom, P. Eline; van Duijn, Cornelia M; Codd, V.; Pedersen, Nancy L; NeuroCHARGE Cognitive Working Group.

In: Translational Psychiatry, Vol. 7, No. 4, 18.04.2017, p. e1100.

Research output: Contribution to JournalArticleAcademicpeer-review

TY - JOUR

T1 - Short telomere length is associated with impaired cognitive performance in European ancestry cohorts

AU - Hägg, S.

AU - Zhan, Y

AU - Karlsson, R.

AU - Gerritsen, L.

AU - Ploner, A.

AU - Lee, J.-S.

AU - Broer, L.

AU - Deelen, J.

AU - Marioni, Riccardo E

AU - Wong, A

AU - Lundquist, A

AU - Zhu, G.

AU - Hansell, Narelle K

AU - Sillanpää, E.

AU - Fedko, I O

AU - Amin, N A

AU - Beekman, M

AU - Craen, A.J.M.

AU - Degerman, S

AU - Harris, S E

AU - Kan, K-J

AU - Martin-Ruiz, C.

AU - Montgomery, Grant W

AU - Adolfsson, A N

AU - Reynolds, C.A.

AU - Samani, Nilesh J

AU - Suchiman, H E D

AU - Viljanen, A

AU - von Zglinicki, T

AU - Wright, Margaret J

AU - Hottenga, J-J

AU - Boomsma, D I

AU - Rantanen, T.

AU - Kaprio, J A

AU - Nyholt, D R

AU - Martin, Nicholas G

AU - Nyberg, L.

AU - Adolfsson, R

AU - Kuh, D

AU - Starr, J. M.

AU - Deary, I. J.

AU - Slagboom, P. Eline

AU - van Duijn, Cornelia M

AU - Codd, V.

AU - Pedersen, Nancy L

AU - NeuroCHARGE Cognitive Working Group

PY - 2017/4/18

Y1 - 2017/4/18

N2 - 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.

AB - 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.

KW - Journal Article

U2 - 10.1038/tp.2017.73

DO - 10.1038/tp.2017.73

M3 - Article

VL - 7

SP - e1100

JO - Translational Psychiatry

JF - Translational Psychiatry

SN - 2158-3188

IS - 4

ER -