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| PMID |
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| TITLE |
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| Short telomere length is associated with impaired cognitive performance in European ancestry cohorts. |
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| ABSTRACT |
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| 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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| DATE PUBLISHED |
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| HISTORY |
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| PUBSTATUS |
PUBSTATUSDATE |
| received |
2017/02/13 |
| accepted |
2017/02/13 |
| entrez |
2017/04/19 06:00 |
| pubmed |
2017/04/19 06:00 |
| medline |
2017/04/19 06:00 |
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| AUTHORS |
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| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Hägg S |
|
Hägg |
S |
S |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Zhan Y |
|
Zhan |
Y |
Y |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Karlsson R |
|
Karlsson |
R |
R |
|
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Gerritsen L |
|
Gerritsen |
L |
L |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| Ploner A |
|
Ploner |
A |
A |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
| van der Lee SJ |
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van der Lee |
S J |
SJ |
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Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. |
| Broer L |
|
Broer |
L |
L |
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Department of Internal Medicine, Erasmus University Medical Center, Rotterdam, The Netherlands. |
| Deelen J |
|
Deelen |
J |
J |
|
Max Planck Institute for Biology of Ageing, Cologne, Germany. |
| Marioni RE |
|
Marioni |
R E |
RE |
|
Queensland Brain Institute, University of Queensland, Brisbane, QLD, Australia. |
| Wong A |
|
Wong |
A |
A |
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MRC Unit for Lifelong Health and Ageing at UCL, London, UK. |
| Lundquist A |
|
Lundquist |
A |
A |
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Department of Statistics, Umeå University, Umeå, Sweden. |
| Zhu G |
|
Zhu |
G |
G |
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QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Hansell NK |
|
Hansell |
N K |
NK |
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QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Sillanpää E |
|
Sillanpää |
E |
E |
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Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland. |
| Fedko IO |
|
Fedko |
I O |
IO |
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Department Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands. |
| Amin NA |
|
Amin |
N A |
NA |
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Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. |
| Beekman M |
|
Beekman |
M |
M |
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Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. |
| de Craen AJM |
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de Craen |
A J M |
AJM |
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Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands. |
| Degerman S |
|
Degerman |
S |
S |
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Department of Medical Biosciences, Umeå University, Umeå, Sweden. |
| Harris SE |
|
Harris |
S E |
SE |
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Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK. |
| Kan KJ |
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Kan |
K-J |
KJ |
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Department Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands. |
| Martin-Ruiz CM |
|
Martin-Ruiz |
C M |
CM |
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NIHR Newcastle Biomedical Research Centre & Unit, Institute of Neurosciences, Newcastle University, Campus for Ageing and Vitality, Newcastle upon Tyne, UK. |
| Montgomery GW |
|
Montgomery |
G W |
GW |
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QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
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NeuroCHARGE Cognitive Working Group |
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| Adolfsson AN |
|
Adolfsson |
A N |
AN |
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Department of Clinical Sciences, Umeå University, Umeå, Sweden. |
| Reynolds CA |
|
Reynolds |
C A |
CA |
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Department of Psychology, University California Riverside, Riverside, CA, USA. |
| Samani NJ |
|
Samani |
N J |
NJ |
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National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. |
| Suchiman HED |
|
Suchiman |
H E D |
HED |
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Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. |
| Viljanen A |
|
Viljanen |
A |
A |
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Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland. |
| von Zglinicki T |
|
von Zglinicki |
T |
T |
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Newcastle University Institute for Ageing, Institute for Cell & Molecular Biosciences, Newcastle upon Tyne, UK. |
| Wright MJ |
|
Wright |
M J |
MJ |
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Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia. |
| Hottenga JJ |
|
Hottenga |
J-J |
JJ |
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Department Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands. |
| Boomsma DI |
|
Boomsma |
D I |
DI |
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Department Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands. |
| Rantanen T |
|
Rantanen |
T |
T |
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Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland. |
| Kaprio JA |
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Kaprio |
J A |
JA |
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National Institute for Health and Welfare (THL), Helsinki, Finland. |
| Nyholt DR |
|
Nyholt |
D R |
DR |
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Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia. |
| Martin NG |
|
Martin |
N G |
NG |
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QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia. |
| Nyberg L |
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Nyberg |
L |
L |
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Umeå center for Functional Brain Imaging, Umeå University, Umeå, Sweden. |
| Adolfsson R |
|
Adolfsson |
R |
R |
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Department of Clinical Sciences, Umeå University, Umeå, Sweden. |
| Kuh D |
|
Kuh |
D |
D |
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MRC Unit for Lifelong Health and Ageing at UCL, London, UK. |
| Starr JM |
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Starr |
J M |
JM |
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Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK. |
| Deary IJ |
|
Deary |
I J |
IJ |
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Department of Psychology, University of Edinburgh, Edinburgh, UK. |
| Slagboom PE |
|
Slagboom |
P E |
PE |
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Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands. |
| van Duijn CM |
|
van Duijn |
C M |
CM |
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Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands. |
| Codd V |
|
Codd |
V |
V |
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National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK. |
| Pedersen NL |
|
Pedersen |
N L |
NL |
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Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden. |
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| INVESTIGATORS |
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| JOURNAL |
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| VOLUME: 7 |
| ISSUE: 4 |
| TITLE: Translational psychiatry |
| ISOABBREVIATION: Transl Psychiatry |
| YEAR: 2017 |
| MONTH: Apr |
| DAY: 18 |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 2158-3188 |
| ISSNTYPE: Electronic |
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| MEDLINE JOURNAL |
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| MEDLINETA: Transl Psychiatry |
| COUNTRY: United States |
| ISSNLINKING: 2158-3188 |
| NLMUNIQUEID: 101562664 |
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| PUBLICATION TYPE |
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| PUBLICATIONTYPE TEXT |
| Journal Article |
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| COMMENTS AND CORRECTIONS |
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| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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| GRANTS |
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| GENERAL NOTE |
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