Australian data project links 1 in 10 ALS cases to genetics
Consortium collects data to improve understanding of disease
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- Australian data links over 10% of ALS cases to known genetic mutations.
- The SALSA-SGC consortium collects data to understand ALS causes and progression.
- The project brings together seven major motor neuron disease research clinics.
More than one in 10 people with amyotrophic lateral sclerosis (ALS) harbor at least one known disease-causing mutation, according to a new profile from the Strategic ALS Australia Systems Genomics Consortium (SALSA-SGC).
The multi-site research consortium brings together major ALS clinics across Australia to collect clinical data and biological samples from people living with the disease and accelerate understanding of its causes, progression, and treatment. The consortium’s flexible governance model allows researchers across institutions to share data and samples, making SALSA-SGC a scalable national resource for ALS research.
Researchers detailed the new profile in the study, “Strategic Amyotrophic Lateral Sclerosis Australia–Systems Genomics Consortium (SALSA-SGC): cohort profile,” published in BMJ Open.
ALS, the most common form of motor neuron disease (MND), is a progressive condition in which motor neurons, the nerve cells that control voluntary movement, degenerate and die. Muscle weakness is the hallmark symptom of ALS, which usually affects one part of the body at first, then spreads to other regions as it becomes more severe.
A 2015 grant of AU$1 million ($690,000) from Motor Neuron Disease Research Australia — funded through the viral 2014 Ice Bucket Challenge — established the SALSA-SGC. The aim was to collect large datasets, combining clinical information with biological samples to better understand the causes and mechanisms of ALS and related MNDs and to support clinical trials.
Large database includes patients, controls
SALSA-SGC brings together seven major MND clinics across five Australian states. In addition to people with a diagnosis of ALS or a related MND, the study includes healthy individuals as controls and, at some sites, people who carry known ALS mutations but have no symptoms.
Clinical data and biological samples are collected about every three months for as long as participants can attend clinic visits. Some sites also ask patients to fill out a comprehensive lifestyle and environmental questionnaire.
Between April 2016 and December 2024, the SALSA-SGC recruited 1,813 participants, comprising 1,386 ALS/MND cases, 388 healthy controls, and 39 others, including asymptomatic mutation carriers and patients later found not to have ALS.
The mean age at symptom onset for those with ALS or another MND was 60.6, and a diagnosis was made a median of 11.6 months after symptoms first emerged.
Of 1,059 cases screened for known ALS mutations, 125 (11.5%) carried at least one. The most common was the C9orf72 repeat expansion, the most common known genetic cause of ALS, found in 70 people (6.6%). Other carriers had mutations in TIA1, SOD1, SPG7, and several other genes.
Information about single nucleotide polymorphisms, or single changes in the genetic code, are available for 1,088 cases and 244 controls. Fewer participants have whole-genome analysis or DNA methylation data, which measures the addition of methyl groups to DNA.
SALSA-SGC genetic data contributed to an international genome-wide association study, which scans the entire genome to identify genetic variants associated with ALS. The study identified 15 common risk locations in the genome.
The data have also been used to study polygenic risk scores, which estimate an individual’s genetic risk based on a combination of genetic variants. One ongoing clinical trial is using the data to detect a specific change in the UNC13A gene and identify eligible participants.
The researchers noted that the SALSA-SGC is not a national registry so, people living in remote regions of the country may be underrepresented. Those diagnosed at a later stage of the disease are also less likely to be referred to the study, they said.
Researchers can explore versions of the data through an open-access online tool that allows queries by age, sex, gene mutation status, and clinical variables. Access to individual-level data is available to research and commercial organizations following review by a scientific committee. Some published data have been deposited in a public database.
“Ongoing efforts aim to expand recruitment into regional Australia and enhance sample processing for cell-based studies,” the team said.
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