Familial clustering of ALS in a population-based resource

Area of Science:

• Genetics
• Neurology
• Epidemiology

Background:

• Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease with an unknown etiology.
• While sporadic cases are common, a familial component is suspected but not fully quantified.

Purpose of the Study:

• To investigate the extent of inherited risk for amyotrophic lateral sclerosis (ALS) mortality.
• To quantify the relative risk (RR) of ALS death among relatives of affected individuals.

Main Methods:

• Analysis of death certificates (DCs) from 1904-2009 for individuals with at least three generations in the Utah Population Database.
• Calculation of RR for ALS death among first- through fifth-degree relatives and spouses compared to matched control cohorts.

Main Results:

• A significantly increased RR of dying with ALS was observed in first-degree relatives (RR = 4.91) and second-degree relatives (RR = 2.85).
• No increased RR was found for third- through fifth-degree relatives or spouses, suggesting limited familial aggregation beyond second-degree relatives.
• A higher proportion of affected first-degree relatives were male.

Conclusions:

• The findings suggest familial clustering of ALS beyond random chance, supporting a genetic contribution.
• The study's use of mortality data from DCs minimizes ascertainment and recall bias.
• The observed pattern of risk among relatives is consistent with genetic inheritance patterns for ALS.