Hidden ancestral links found in motor neuron disease and dementia could speed up gene discovery
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Researchers at the Macquarie University Brain Institute and Clinic have helped accelerate the search for disease-causing genes by building new genetic 'families.' The team uncovered hundreds of previously unrecognized family connections by analyzing the DNA of people with frontotemporal dementia (FTD) and motor neuron disease (MND).
The researchers analyzed genetic data from 3,524 people with FTD and MND (also known as amyotrophic lateral sclerosis or ALS) from Australia, New Zealand and the United Kingdom. They then identified relatives ranging from siblings to third cousins using a technique called cryptic relatedness analysis.
Lead author Dr. Lyndal Henden says these relationships can be difficult to recognize in adult-onset diseases like ALS and FTD because not everyone who carries a genetic variant linked to disease develops symptoms, and family histories may be incomplete.
"Family history does not always tell the whole story in MND and FTD," Henden says. "People who appear unrelated can share DNA inherited from a common ancestor, and bringing these people together into genetic families gives us more information to work with when searching for the causes of disease."
The research published in the journal Brain identified 793 related pairs within the cohort and more than 30% previously unrecognized relationships.
These hidden relationships allowed the researchers to build 73 new DNA-based family trees from people who had no known genetic explanation for their disease, giving researchers larger families to help track down new disease-linked variants.
"Where we might have had only one person to study, we can now compare affected relatives and prioritize the regions of DNA they inherited from the same ancestor," said senior author professor Kelly Williams.
The researchers also mapped shared ancestry around known ALS/FTD genes. This revealed 'founder' networks, where people carry the same genetic change (including the known disease-linked SOD1 and C9orf72 genes) because they inherited it from a shared distant ancestor. These networks connected seemingly unrelated families, including people with sporadic disease, across Australia, New Zealand and the United Kingdom.
The study also showed why traditional labels of 'familial' and 'sporadic' disease do not always capture the underlying genetics. Among people recorded clinically as having sporadic disease, almost 16% of people with FTD and 5.5% of people with ALS were genetically related to another affected person in the cohort. Some genetically related individuals also had different diagnoses, highlighting how shared genetic backgrounds can show up in different ways.
"This kind of analysis helps us find family connections that conventional family histories can miss," Williams said. "By reconstructing those families genetically, we can make much better use of existing patient cohorts to search for new disease genes and understand why the same inherited genetic background can lead to very different outcomes."
Publication details
Lyndal Henden et al., Identity-by-descent to resolve reduced penetrance and advance gene discovery in neurodegenerative disease, Brain (2026). DOI: 10.1093/brain/awag326
Journal information: Brain
Key medical concepts
Motor Neuron DiseaseFrontotemporal DementiaSuperoxide Dismutase [Cu-Zn]C9orf72-SMCR8 complex subunit
Clinical categories
NeurologyClinical genetics Provided by Macquarie University Who's behind this story?
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Citation: Hidden ancestral links found in motor neuron disease and dementia could speed up gene discovery (2026, November 3) retrieved 3 November 2026 from https://medicalxpress.com/news/2026-11-hidden-ancestral-links-motor-neuron.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.