Abstract: Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis (ALS) as globally rising fatal disorders with the highest prevalence in aging populattons, influenced by ethnicity and ancestry (GBD 2016 Motor Neuron Disease Collaborators, 2018). While ~10% of diagnoses involve a family history (fALS), most cases are considered sporadic (sALS). However, population-based studies suggest that even cases without a common index mutation impart heritability (Ryan et al., 2019), indicating a crucial role of rare and as yet unknown genettc denominators. Genotype-phenotype predictions remain weak despite an ever-rising resolution of background genetics and propose overlap in the (oligo-)genic architecture of simplified fALS and sALS categories. Establishing a new class of genetic biomarkers sensitive to both fALS and nominal sALS would impart paramount value in accelerating diagnosis, ascertaining patient strattffcattons, and improving predictton of disease progression.