Genetic Epidemiology, Psychiatric Genetics, Asthma Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
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PMID
28418400
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.
DATE PUBLISHED
2017 Apr 18
HISTORY
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
AUTHORS
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 Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
Ploner A Ploner A A Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
van der Lee SJ van der Lee S J SJ Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Broer L Broer L L 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 MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
Lundquist A Lundquist A A Department of Statistics, Umeå University, Umeå, Sweden.
Zhu G Zhu G G QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Hansell NK Hansell N K NK QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Sillanpää E Sillanpää E E Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
Fedko IO Fedko I O IO Department Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
Amin NA Amin N A NA Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Beekman M Beekman M M Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
de Craen AJM de Craen A J M AJM Department of Gerontology and Geriatrics, Leiden University Medical Center, Leiden, The Netherlands.
Degerman S Degerman S S Department of Medical Biosciences, Umeå University, Umeå, Sweden.
Harris SE Harris S E SE Centre for Cognitive Ageing and Cognitive Epidemiology, University of Edinburgh, Edinburgh, UK.
Kan KJ Kan K-J KJ Department Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
Martin-Ruiz CM Martin-Ruiz C M CM 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 QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
NeuroCHARGE Cognitive Working Group
Adolfsson AN Adolfsson A N AN Department of Clinical Sciences, Umeå University, Umeå, Sweden.
Reynolds CA Reynolds C A CA Department of Psychology, University California Riverside, Riverside, CA, USA.
Samani NJ Samani N J NJ National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Suchiman HED Suchiman H E D HED Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
Viljanen A Viljanen A A Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
von Zglinicki T von Zglinicki T T Newcastle University Institute for Ageing, Institute for Cell & Molecular Biosciences, Newcastle upon Tyne, UK.
Wright MJ Wright M J MJ Centre for Advanced Imaging, University of Queensland, Brisbane, QLD, Australia.
Hottenga JJ Hottenga J-J JJ Department Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
Boomsma DI Boomsma D I DI Department Biological Psychology, Vrije Universiteit, Amsterdam, The Netherlands.
Rantanen T Rantanen T T Gerontology Research Center, Faculty of Sport and Health Sciences, University of Jyväskylä, Jyväskylä, Finland.
Kaprio JA Kaprio J A JA National Institute for Health and Welfare (THL), Helsinki, Finland.
Nyholt DR Nyholt D R DR Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane, QLD, Australia.
Martin NG Martin N G NG QIMR Berghofer Medical Research Institute, Brisbane, QLD, Australia.
Nyberg L Nyberg L L Umeå center for Functional Brain Imaging, Umeå University, Umeå, Sweden.
Adolfsson R Adolfsson R R Department of Clinical Sciences, Umeå University, Umeå, Sweden.
Kuh D Kuh D D MRC Unit for Lifelong Health and Ageing at UCL, London, UK.
Starr JM Starr J M JM Alzheimer Scotland Dementia Research Centre, University of Edinburgh, Edinburgh, UK.
Deary IJ Deary I J IJ Department of Psychology, University of Edinburgh, Edinburgh, UK.
Slagboom PE Slagboom P E PE Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands.
van Duijn CM van Duijn C M CM Department of Epidemiology, Erasmus University Medical Center, Rotterdam, The Netherlands.
Codd V Codd V V National Institute for Health Research Leicester Cardiovascular Biomedical Research Unit, Glenfield Hospital, Leicester, UK.
Pedersen NL Pedersen N L NL Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
INVESTIGATORS
JOURNAL
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
MEDLINE JOURNAL
MEDLINETA: Transl Psychiatry
COUNTRY: United States
ISSNLINKING: 2158-3188
NLMUNIQUEID: 101562664
PUBLICATION TYPE
PUBLICATIONTYPE TEXT
Journal Article
COMMENTS AND CORRECTIONS
REFTYPE REFSOURCE REFPMID NOTE
Cites Mol Psychiatry. 2015 Feb;20(2):183-92 25644384
Cites Int J Epidemiol. 2015 Apr;44(2):578-86 26016847
Cites Eur J Epidemiol. 2016 Feb;31(2):147-57 26076919
Cites Proc Natl Acad Sci U S A. 2014 Apr 22;111(16):5944-9 24711381
Cites Nature. 2011 Jan 6;469(7328):102-6 21113150
Cites Mech Ageing Dev. 2016 Mar;154:43-8 26876762
Cites Blood Purif. 2016;41(1-3):25-33 26960211
Cites Int J Epidemiol. 2014 Jun;43(3):878-86 24425829
Cites Neurobiol Aging. 2011 Nov;32(11):2055-60 20031273
Cites Arch Neurol. 2012 Oct;69(10):1332-9 22825311
Cites Epidemiol Rev. 2013;35:33-50 23349427
Cites Nucleic Acids Res. 2014 Jan;42(Database issue):D1001-6 24316577
Cites BMJ. 2012 Nov 06;345:e7325 23131671
Cites Science. 2015 Dec 4;350(6265):1193-8 26785477
Cites Psychol Aging. 2007 Sep;22(3):558-68 17874954
Cites Curr Biol. 2015 May 4;25(9):1146-56 25913401
Cites Eur J Epidemiol. 2015 Jul;30(7):543-52 25773750
Cites J Neurol Sci. 2010 Dec 15;299(1-2):108-11 20709332
Cites Mol Psychiatry. 2016 Nov;21(11):1624-1632 26809841
Cites Int J Epidemiol. 2011 Jun;40(3):626-44 21037248
Cites PLoS One. 2012;7(4):e34292 22506016
Cites PLoS One. 2014 Dec 12;9(12):e113387 25501556
Cites Int J Epidemiol. 2013 Aug;42(4):1134-44 24062299
Cites Neurobiol Aging. 2010 Apr;31(4):719-20 18599157
Cites Neurobiol Aging. 2012 Feb;33(2):335-44 20395015
Cites JAMA Neurol. 2015 Oct;72(10):1202-3 26457630
Cites Aging Cell. 2007 Dec;6(6):769-74 17925004
Cites Neurosci Lett. 2011 Mar 29;492(1):15-8 21295115
Cites Nat Genet. 2013 Apr;45(4):422-7, 427e1-2 23535734
Cites Mol Psychiatry. 2016 Feb;21(2):189-97 25869804
Cites Neuropsychology. 2013 Jul;27(4):391-401 23876113
Cites Am J Epidemiol. 2011 Jun 15;173(12):1392-403 21555716
Cites Am J Epidemiol. 2009 Feb 1;169(3):323-9 19056834
Cites Hum Mol Genet. 2015 Sep 15;24(18):5356-66 26138067
Cites Nucleic Acids Res. 2002 May 15;30(10):e47 12000852
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