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  • Hagg, SKarolinska Institutet (author)

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

  • Article/chapterEnglish2017

Publisher, publication year, extent ...

  • 2017-04-18
  • Springer Science and Business Media LLC,2017

Numbers

  • LIBRIS-ID:oai:prod.swepub.kib.ki.se:135958451
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:135958451URI
  • https://doi.org/10.1038/tp.2017.73DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-136343URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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.

Subject headings and genre

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  • Zhan, YKarolinska Institutet (author)
  • Karlsson, RKarolinska Institutet (author)
  • Gerritsen, L (author)
  • Ploner, AKarolinska Institutet (author)
  • van der Lee, SJ (author)
  • Broer, L (author)
  • Deelen, J (author)
  • Marioni, RE (author)
  • Wong, A (author)
  • Lundquist, AndersUmeå universitet,Statistik(Swepub:umu)anslst97 (author)
  • Zhu, G (author)
  • Hansell, NK (author)
  • Sillanpaa, E (author)
  • Fedko, IO (author)
  • Amin, NA (author)
  • Beekman, M (author)
  • de Craen, AJM (author)
  • Degerman, SofieUmeå universitet,Patologi(Swepub:umu)soiden99 (author)
  • Harris, SE (author)
  • Kan, KJ (author)
  • Martin-Ruiz, CM (author)
  • Montgomery, GW (author)
  • Adolfsson, Annelie N.Umeå universitet,Psykiatri(Swepub:umu)anenon01 (author)
  • Reynolds, CA (author)
  • Samani, NJ (author)
  • Suchiman, HED (author)
  • Viljanen, A (author)
  • von Zglinicki, T (author)
  • Wright, MJ (author)
  • Hottenga, JJ (author)
  • Boomsma, DI (author)
  • Rantanen, T (author)
  • Kaprio, JA (author)
  • Nyholt, DR (author)
  • Martin, NG (author)
  • Nyberg, LarsKarolinska Institutet,Umeå universitet,Institutionen för strålningsvetenskaper,Institutionen för integrativ medicinsk biologi (IMB),Umeå centrum för funktionell hjärnavbildning (UFBI)(Swepub:umu)lany0001 (author)
  • Adolfsson, RolfUmeå universitet,Psykiatri(Swepub:umu)road0001 (author)
  • Kuh, D (author)
  • Starr, JM (author)
  • Deary, IJ (author)
  • Slagboom, PE (author)
  • van Duijn, CM (author)
  • Codd, V (author)
  • Pedersen, NLKarolinska Institutet (author)
  • Karolinska InstitutetStatistik (creator_code:org_t)

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