Oligogenic structure of amyotrophic lateral sclerosis has genetic testing, counselling and therapeutic implications.

ABSTRACT:

Background

Despite several studies suggesting a potential oligogenic risk model in amyotrophic lateral sclerosis (ALS), case-control statistical evidence implicating oligogenicity with disease risk or clinical outcomes is limited. Considering its direct clinical and therapeutic implications, we aim to perform a large-scale robust investigation of oligogenicity in ALS risk and in the disease clinical course.

Methods

We leveraged Project MinE genome sequencing datasets (6711 cases and 2391 controls) to identify associations between oligogenicity in known ALS genes and disease risk, as well as clinical outcomes.

Results

In both the discovery and replication cohorts, we observed that the risk imparted from carrying multiple ALS rare variants was significantly greater than

SUBMITTER: Iacoangeli A 

PROVIDER: S-EPMC12505044 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature