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

Population-based genome-wide association study of cognitive decline in older adults free of dementia: identification of a novel locus for the attention domain. Neurobiol Aging. 2019 Mar 11;: Authors: Kamboh MI, Fan KH, Yan Q, Beer JC, Snitz BE, Wang X, Chang CH, Demirci FY, Feingold E, Ganguli M Abstract To 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....
Source: Neurobiology of Aging - Category: Geriatrics Authors: Tags: Neurobiol Aging Source Type: research