Hidden ancestral links found in motor neuron disease and dementia could speed up gene discovery

Researchers at the Macquarie University Brain Institute and Clinic have identified hidden ancestral links between motor neuron disease (MND) and dementia, potentially accelerating the discovery of disease-causing genes. By analyzing genetic data from 3,524 individuals with frontotemporal dementia (FTD) and motor neuron disease (also known as ALS or amyotrophic lateral sclerosis), the team uncovered hundreds of unrecognized family connections.

Using a technique called cryptic relatedness analysis, the researchers identified relatives ranging from siblings to third cousins, some of whom may not have been related based on traditional family histories. These hidden relationships allowed the researchers to build 73 new DNA-based family trees, providing a larger pool of individuals for further genetic research.

The study, published in the journal Brain, also revealed previously unrecognized relationships among previously unrelated individuals, showing how shared genetic backgrounds can present in different ways. This approach helped identify 793 related pairs and over 30% of previously unrecognized relationships, allowing researchers to compare affected relatives and prioritize regions of DNA inherited from the same ancestor.

Furthermore, the analysis connected seemingly unrelated families through shared ancestry around known ALS/FTD genes, revealing "founder networks" where people carry the same genetic changes due to inheritance from a distant shared ancestor. This method highlighted how traditional labels of familial and sporadic disease do not always capture the underlying genetics.

The researchers believe that using genetic data to reconstruct these families can lead to better utilization of existing patient cohorts for discovering new disease genes and understanding why the same inherited genetic background can result in diverse outcomes.