Genetics of Amyotrophic Lateral Sclerosis

Jenna Gregory* (Corresponding Author), Delphine Fagegaltier, Hemali Phatnani* (Corresponding Author), Matthew B. Harms* (Corresponding Author)

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

3 Downloads (Pure)


Purpose of Review
Amyotrophic lateral sclerosis and frontotemporal dementia (ALS-FTD) spectrum disorder is a rare fatal disease with strong genetic influences. The implementation of short-read sequencing methodologies in increasingly large patient cohorts has rapidly expanded our knowledge of the complex genetic architecture of the disease. We aim to convey the broad history of ALS gene discovery as context for a focused review of 11 ALS gene associations reported over the last 5 years. We also summarize the current level of genetic evidence for all previously reported genes.

Recent Findings
The history of ALS gene discovery has occurred in at least four identifiable phases, each powered by different technologies and scale of investigation. The most recent epoch, benefitting from population-scale genome data, large international consortia, and low-cost sequencing, has yielded 11 new gene associations. We summarize the current level of genetic evidence supporting these ALS genes, highlighting any genotype-phenotype or genotype-pathology correlations, and discussing preliminary understanding of molecular pathogenesis. This era has also raised uncertainty around prior ALS-associated genes and clarified the role of others.

Our understanding of the genetic underpinning of ALS has expanded rapidly over the last 25 years and has led directly to the clinical application of molecularly driven therapies. Ongoing sequencing efforts in ALS will identify new causative and risk factor genes while clarifying the status of genes reported in prior eras of research.
Original languageEnglish
Pages (from-to)121-131
JournalCurrent Genetic Medicine Reports
Early online date7 Nov 2020
Publication statusPublished - Dec 2020


  • Human genetics
  • Amyotrophic lateral sclerosis
  • Frontotemporal dementia
  • Neurodegenerative disease
  • ALS genes
  • ALS genetics


Dive into the research topics of 'Genetics of Amyotrophic Lateral Sclerosis'. Together they form a unique fingerprint.

Cite this