Abstract Details

Title Heritability of ALS: A Population-based study over 24 years.

Topic Neuromuscular and Clinical Neurophysiology (EMG)

Presentation(s) S54 - Motor Neuron Disease (3:30 PM-3:41 PM)

Poster/Presentation
Number 001

Background Heritability describes the proportion of risk of developing a condition that is explained by genetic factors. ALS is known to be of complex genetic origin, but the heritability of the disease remains unclear. To resolve this question, we have conducted the largest population-based study of ALS heritability to date.

Objective

To determine the heritability of Amyotrophic Lateral Sclerosis (ALS).

Design/Methods Using data from the Irish ALS register, between 2008 and 2017, we calculated 1) age-adjusted lifetime risks of developing ALS, 2) ALS concordance rates in parent-offspring pairs and 3) overall and sex-specific ALS heritability estimates.

Results 1117 Irish patients with ALS were included in the study. The lifetime risk of developing ALS in the Irish population is 2.88 and 2.29 per 1,000 men and women respectively, corresponding to 1 in 347 men and 1 in 436 women. The total lifetime risk of developing ALS is 1.43% in any first-degree relative of those with ALS. Overall, the heritability of ALS is between 40-50%, adjusted for the underlying age and sex structure of the population. Heritability estimates of over 70% were observed in female parent-offspring concordant pairs, a previously unrecognized sex-specific effect.

Conclusions Genetic factors account for close to 50% of the risk for developing ALS. Notwithstanding, while the risk of developing ALS in first-degree relatives of those affected is increased, in the absence of a known Mendelian inherited gene, the overall risk to relatives is low. However, genetic factors likely play a greater role in the development of the disease among female patients.

Authors/Disclosures
PRESENTER	No disclosure on file
	No disclosure on file
Niall Pender, PhD	No disclosure on file
	No disclosure on file
Orla Hardiman, MD, FRCPI, FAAN (Trinity Biomedical Sciences Institute)	Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Wave Pharmaceuticals. Dr. Hardiman has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Cytokinetics . Dr. Hardiman has received personal compensation in the range of $0-$499 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Hardiman has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Taylor and Francis. The institution of Dr. Hardiman has received research support from Science Foundation Ireland. The institution of Dr. Hardiman has received research support from HRB.

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