Genome-wide analyses identify NEAT1 as genetic modifier of age at onset of amyotrophic lateral sclerosis.

ABSTRACT:

Background

Patients with amyotrophic lateral sclerosis (ALS) demonstrate great heterogeneity in the age at onset (AAO), which is closely related to the course of disease. However, most genetic studies focused on the risk of ALS, while the genetic background underlying AAO of ALS is still unknown.

Methods

To identify genetic determinants influencing AAO of ALS, we performed genome-wide association analysis using a Cox proportional hazards model in 2,841 patients with ALS (N_discovery = 2,272, N_replication = 569) in the Chinese population. We further conducted colocalization analysis using public cis-eQTL dataset, and Mendelian randomization analysis to identify risk factors for AAO of ALS. Finally, functional experiments including dual-luciferase reporter

SUBMITTER: Li C 

PROVIDER: S-EPMC10594666 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature