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

• Published in: Brain imaging and behavior 2020-02, Vol.14 (1), p.213-225
• Main Authors: de Vries, Clarisse F., Staff, Roger T., Noble, Kimberly G., Muetzel, Ryan L., Vernooij, Meike W., White, Tonya, Waiter, Gordon D., Murray, Alison D.
• Format: Article
• Language: English
• Subjects: Adolescents; Age; Biomedical and Life Sciences; Biomedicine; Brain; Children; Cognition; Cognition & reasoning; Cognitive ability; Executive function; Gene polymorphism; Girls; Heterozygotes; Klotho protein; Memory; Morphology; Neuropsychology; Neuroradiology; Neurosciences; Original Research; Polymorphism; Psychiatry; Sex; Substantia alba; Substantia grisea
• ISSN: 1931-7557; 1931-7565
• DOI: 10.1007/s11682-018-9990-1

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.