Repeat variations in polyglutamine disease-associated genes and cognitive function in old age.

Autor: Gardiner SL; Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands; Department of Human Genetics, Leiden University Medical Centre, Leiden, the Netherlands. Electronic address: s.l.gardiner@lumc.nl., Trompet S; Department of Internal Medicine, Section of Gerontology and Geriatrics, Leiden University Medical Centre, Leiden, the Netherlands., Sabayan B; The Ken and Ruth Davee Department of Neurology, Northwestern University, Chicago, IL, USA., Boogaard MW; Department of Clinical Genetics, Leiden University Medical Centre, Leiden, the Netherlands., Jukema JW; Department of Cardiology, Leiden University Medical Centre, Leiden, the Netherlands., Slagboom PE; Department of Molecular Epidemiology, Leiden University Medical Centre, Leiden, the Netherlands., Roos RAC; Department of Neurology, Leiden University Medical Centre, Leiden, the Netherlands., van der Grond J; Department of Radiology, Leiden University Medical Centre, Leiden, the Netherlands., Aziz NA; Population Health Sciences, German Centre for Neurodegenerative Diseases (DZNE), Bonn, Germany; Department of Neurology, University of Bonn, Bonn, Germany.
Jazyk: angličtina
Zdroj: Neurobiology of aging [Neurobiol Aging] 2019 Dec; Vol. 84, pp. 236.e17-236.e28. Date of Electronic Publication: 2019 Aug 09.
DOI: 10.1016/j.neurobiolaging.2019.08.002
Abstrakt: Although the heritability of cognitive function in old age is substantial, genome-wide association studies have had limited success in elucidating its genetic basis, leaving a considerable amount of "missing heritability." Aside from single nucleotide polymorphisms, genome-wide association studies are unable to assess other large sources of genetic variation, such as tandem repeat polymorphisms. Therefore, here, we studied the association of cytosine-adenine-guanine (CAG) repeat variations in polyglutamine disease-associated genes (PDAGs) with cognitive function in older adults. In a large cohort consisting of 5786 participants, we found that the CAG repeat number in 3 PDAGs (TBP, HTT, and AR) were significantly associated with the decline in cognitive function, which together accounted for 0.49% of the variation. Furthermore, in an magnetic resonance imaging substudy, we found that CAG repeat polymorphisms in 4 PDAGs (ATXN2, CACNA1A, ATXN7, and AR) were associated with different imaging characteristics, including brain stem, putamen, globus pallidus, thalamus, and amygdala volumes. Our findings indicate that tandem repeat polymorphisms are associated with cognitive function in older adults and highlight the importance of PDAGs in elucidating its missing heritability.
(Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
Databáze: MEDLINE
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