Combined epigenetic/genetic study identified an ALS age of onset modifier.

ABSTRACT: Age at onset of amyotrophic lateral sclerosis (ALS) is highly variable (eg, 27-74 years in carriers of the G₄C₂-expansion in C9orf72). It might be influenced by environmental and genetic factors via the modulation of DNA methylation (DNAm) at CpG-sites. Hence, we combined an epigenetic and genetic approach to test the hypothesis that some common single nucleotide polymorphisms (SNPs) at CpG-sites (CpG-SNPs) could modify ALS age of onset. Our genome-wide DNAm analysis suggested three CpG-SNPs whose DNAm levels are significantly associated with age of onset in 249 ALS patients (q < 0.05). Next, genetic analysis validated the association of rs4970944 with age of onset in the discovery (n = 469; P = 0.025) and replication (n = 4160; P = 0.007) ALS cohorts. A meta-analysis

SUBMITTER: Zhang M 

PROVIDER: S-EPMC8066440 | biostudies-literature | 2021 Apr

REPOSITORIES: biostudies-literature