Genome-wide association analysis of cognitive function in Danish long-lived individuals

Marianne Nygaard, Joseph Dowsett, Matt McGue, Kaare Christensen, Lene Christiansen, Qihua Tan, Jonas Mengel-From

Research output: Contribution to journalArticlepeer-review


Cognitive function is a substantially heritable trait related to numerous important life outcomes. Several genome-wide association studies of cognitive function have in recent years led to the identification of thousands of significantly associated loci and genes. Individuals included in these studies have rarely been nonagenarians and centenarians, and since cognitive function is an important component of quality of life for this rapidly expanding demographic group, there is a need to explore genetic factors associated with individual differences in cognitive function at advanced ages. In this study, we pursued this by performing a genome-wide association study of cognitive function in 490 long-lived Danes (age range 90.1-100.8 years). While no genome-wide significant SNPs were identified, suggestively significant SNPs (P < 1 × 10 -5) were mapped to several interesting genes, including ZWINT, CELF2, and DNAH5, and the glutamate receptor genes GRID2 and GRM7. Additionally, results from a gene set over-representation analysis indicated potential roles of gene sets related to G protein-coupled receptor (GPCR) signaling, interaction between L1 and ankyrins, mitogen-activated protein kinase (MAPK) signaling, RNA degradation, and cell cycle. Larger studies are needed to shed further light on the possible importance of these suggestive genes and pathways in cognitive function in nonagenarians and centenarians.

Original languageEnglish (US)
Article number111463
JournalMechanisms of Ageing and Development
StatePublished - Apr 2021

Bibliographical note

Funding Information:
This study was financially supported by The National Program for Research Infrastructure 2007 (grant no. 09-063256 ), the Danish Agency for Science Technology and Innovation , the Velux Foundation , the US National Institute of Health ( P01 AG08761 ), the Danish Agency for Science, Technology and Innovation/The Danish Council for Independent Research (grant no. 11-107308 ), The Danish Interdisciplinary Research Council , the European Union's Seventh Framework Programme ( FP7/2007-2011 ) under grant agreement n° 259679 , and the INTERREG 4 A programme Syddanmark-Schleswig-K.E.R.N. (by EU funds from the European Regional Development Fund ).

Publisher Copyright:
© 2021 Elsevier B.V.


  • Cognitive function
  • Gene-based analysis
  • Genome-wide association study
  • Long-lived individuals
  • Pathway analysis

PubMed: MeSH publication types

  • Journal Article
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't


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