Large-scale exploratory genetic analysis of cognitive impairment in Parkinson's disease

Neurobiology of Aging
Ignacio F MataC P Zabetian

Abstract

Cognitive impairment is a common and disabling problem in Parkinson's disease (PD). Identification of genetic variants that influence the presence or severity of cognitive deficits in PD might provide a clearer understanding of the pathophysiology underlying this important nonmotor feature. We genotyped 1105 PD patients from the PD Cognitive Genetics Consortium for 249,336 variants using the NeuroX array. Participants underwent assessments of learning and memory (Hopkins Verbal Learning Test-Revised [HVLT-R]), working memory/executive function (Letter-Number Sequencing and Trail Making Test [TMT] A and B), language processing (semantic and phonemic verbal fluency), visuospatial abilities (Benton Judgment of Line Orientation [JoLO]), and global cognitive function (Montreal Cognitive Assessment). For common variants, we used linear regression to test for association between genotype and cognitive performance with adjustment for important covariates. Rare variants were analyzed using the optimal unified sequence kernel association test. The significance threshold was defined as a false discovery rate-corrected p-value (PFDR) of 0.05. Eighteen common variants in 13 genomic regions exceeded the significance threshold for one of the ...Continue Reading

Citations

Oct 6, 2020·Frontiers in Neurology·Douglas N MartiniFay Horak
Sep 5, 2020·NPJ Parkinson's Disease·Thanaphong PhongpreechaThomas J Montine
Apr 26, 2018·Frontiers in Neuroscience·Laura IbanezBruno A Benitez
Oct 19, 2017·Neurological Sciences : Official Journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology·Costanza Papagno, Luigi Trojano
Oct 7, 2020·Neuropsychology, Development, and Cognition. Section B, Aging, Neuropsychology and Cognition·Ece BayramDeborah L Harrington
Feb 15, 2021·Annals of Neurology·Yann Le GuenMichael D Greicius
Aug 26, 2021·NPJ Parkinson's Disease·Thanaphong PhongpreechaThomas J Montine

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