A genome-wide association study identifies the GPM6A locus associated with age at onset in ALS.

ABSTRACT: Amyotrophic lateral sclerosis (ALS) exhibits considerable clinical variability, such as differences in age at onset (AAO). Multiple factors, including genetic factors, may underlie this variability; however, the specific determinants remain unclear. To identify genes affecting AAO, we have conducted a genome-wide association study in Japanese patients with ALS (discovery cohort: n = 1808; replication cohort: n = 207). Here, we show that the minor A allele of rs113161727 at the ADAM29-GPM6A locus is associated with a younger AAO in the discovery cohort (effect, -4.27 years; p = 4.60 × 10^-8); this finding has been confirmed in the replication cohort (p = 0.0068) and meta-analysis (p = 1.08 × 10^-9). Among 65 ALS patients with a SOD1 mutation, the AAO has been found to be

SUBMITTER: Nakamura R 

PROVIDER: S-EPMC12680644 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature