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Klotho gene polymorphism, brain structure and cognition in early-life development.

Authors
  • de Vries, Clarisse F1
  • Staff, Roger T2
  • Noble, Kimberly G3
  • Muetzel, Ryan L4, 5, 6
  • Vernooij, Meike W5, 6, 7
  • White, Tonya4, 6, 7
  • Waiter, Gordon D1
  • Murray, Alison D1
  • 1 Aberdeen Biomedical Imaging Centre, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Foresterhill, Aberdeen, AB25 2ZD, UK.
  • 2 Imaging Physics, Aberdeen Royal Infirmary, NHS Grampian, Foresterhill, Aberdeen, AB25 2ZD, UK. [email protected]
  • 3 Teachers College, Columbia University, New York, NY, 10027, USA.
  • 4 Department of Child and Adolescent Psychiatry, Erasmus University Medical Centre, Rotterdam, Netherlands. , (Netherlands)
  • 5 Department of Epidemiology, Erasmus University Medical Center, Rotterdam, Netherlands. , (Netherlands)
  • 6 The Generation R Study Group, Erasmus Medical Center, Rotterdam, The Netherlands. , (Netherlands)
  • 7 Department of Radiology and Nuclear Medicine, Erasmus University Medical Centre, Rotterdam, Netherlands. , (Netherlands)
Type
Published Article
Journal
Brain Imaging and Behavior
Publisher
Springer-Verlag
Publication Date
Feb 01, 2020
Volume
14
Issue
1
Pages
213–225
Identifiers
DOI: 10.1007/s11682-018-9990-1
PMID: 30393836
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Variation in the klotho gene is linked to differences in health outcomes: klotho allele KL-VS heterozygosity is associated with longevity, better cognition and greater right frontal grey matter volume in late life. Contradicting reports, however, suggest that KL-VS's effect on health might be age-dependent. Here we examine the relationship between KL-VS genotype, cognition and brain structure in childhood and adolescence. We hypothesized that KL-VS has early influences on cognitive and brain development. We investigated the associations of KL-VS carrier status with cognition and brain morphology in a cohort of 1387 children and adolescents aged 3-21 years, examining main effects and interactions between age, sex and socioeconomic circumstance. KL-VS had no main effect on either cognition or brain structure, though there was a significant KL-VS × age interaction for cognition (specifically executive function, attention, episodic memory, and general cognition), total grey matter and total brain volume. KL-VS heterozygotes had better cognition than non-carriers before age 11, but lower cognition after age 11. Heterozygotes had smaller brains than non-carriers did in early childhood. Sex moderated the association between KL-VS and white matter volume. Among girls, KL-VS heterozygotes had smaller white matter volumes than non-carriers. Among boys, heterozygotes had greater white matter volumes than non-carriers. However, a replication in a cohort of 2306 children aged 6-12 years showed no significant associations. In contrast to findings in late life, these results show that KL-VS does not have a main effect on cognition and brain structure. Furthermore, KL-VS's influence may depend on age and sex.

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