• Neurobiology of aging · Dec 2019

    Population-based genome-wide association study of cognitive decline in older adults free of dementia: identification of a novel locus for the attention domain.

    • M Ilyas Kamboh, Kang-Hsien Fan, Qi Yan, Joanne C Beer, Beth E Snitz, Xingbin Wang, ChangChung-Chou HCHDepartment of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Medicine, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA., F Yesim Demirci, Eleanor Feingold, and Mary Ganguli.
    • Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Epidemiology, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Psychiatry, School of Medicine, University of Pittsburgh, Pittsburgh, PA, USA. Electronic address: kamboh@pitt.edu.
    • Neurobiol. Aging. 2019 Dec 1; 84: 239.e15-239.e24.

    AbstractTo identify novel loci that affect cognitive decline in older adults free of dementia, we conducted genome-wide and gene-based meta-analyses on longitudinal slopes of 5 cognitive domains (memory, executive function, language, attention/processing speed, and visuospatial ability) derived from 2 population-based cohorts. For decline over time in each cognitive domain, we normalized intraindividual slopes within each cohort, accounting for baseline age, sex, and years of education. Normalized slope for each domain was used in cohort-specific genome-wide analyses after including top principal components as covariates followed by genome-wide and gene-based meta-analyses. Both analyses revealed a novel WDFY2 locus at genome-wide (p = 3.37E-08) and gene-wide (p = 7.10E-07) significance levels for the attention/processing speed domain. In the GTEx eQTL analysis, genome-wide significant single-nucleotide polymorphism was associated with RNA expression levels of WDFY2 in several brain regions: cerebellar hemisphere (p = 1.07E-04), cerebellum (p = 6.92E-04), hippocampus (p = 2.18E-03) and cortex (p = 2.29E-02), and in whole blood (p = 4.41E-05). Our results suggest that WDFY2 genetic variation may affect individual differences in decline over time on tests of attention/processing speed.Copyright © 2019 Elsevier Inc. All rights reserved.

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