Genome-wide association study of rate of cognitive decline in Alzheimer's disease patients identifies novel genes and pathways.

ABSTRACT:

Introduction

Variability exists in the disease trajectories of Alzheimer's disease (AD) patients. We performed a genome-wide association study to examine rate of cognitive decline (ROD) in patients with AD.

Methods

We tested for interactions between genetic variants and time since diagnosis to predict the ROD of a composite cognitive score in 3946 AD cases and performed pathway analysis on the top genes.

Results

Suggestive associations (P < 1.0 × 10^-6 ) were observed on chromosome 15 in DNA polymerase-? (rs3176205, P = 1.11 × 10^-7 ), chromosome 7 (rs60465337,P = 4.06 × 10^-7 ) in contactin-associated protein-2, in RP11-384F7.1 on chromosome 3 (rs28853947, P = 5.93 × 10^-7 ), family with sequence similarity 214 member-A on chromosome 15 (rs2899492, P = 5.94 × 10^-7 ), and intergenic regions on chromosomes 16 (rs4949142, P = 4.02 × 10^-7 ) and 4 (rs1304013, P = 7.73 × 10^-7 ). Significant pathways involving neuronal development and function, apoptosis, memory, and inflammation were identified.

Discussion

Pathways related to AD, intelligence, and neurological function determine AD progression, while previously identified AD risk variants, including the apolipoprotein (APOE) ?4 and ?2 variants, do not have a major impact.

SUBMITTER: Sherva R 

PROVIDER: S-EPMC7924136 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature