Genetic factors account for about half the risk of developing amyotrophic lateral sclerosis (ALS), suggest the findings of a large prospective population-based study published in JAMA Neurology.
The study - the first to assess heritability in the context of known gene mutations of large effect - included 1,117 people diagnosed with ALS.
Annual age-specific and sex-specific standardised ALS incidence and mortality-adjusted lifetime risk were determined. Sex-specific heritability estimates were calculated for the overall cohort, for those known to carry the C9orf72 (OMIM 614260) variant and for those with no known genetic risk.
A total of 32 parent-child ALS dyads were identified during the study period. Affected offspring were younger at disease onset (mean age 52.0 years; 95% CI 48.8-55.3 years) compared with their parents (mean age 69.6 years; 95% CI 62.4-76.9 years: P=.008).
Lifetime risk of developing ALS in the first-degree relatives of individuals with ALS was increased compared with the general population (1.4% vs 0.3%; P<.001>
Mean lifetime heritability of ALS for the overall study cohort was 52.3 per cent (95% CI 42.9%-61.7%) and 36.9 per cent (95% CI 19.8%-53.9%) in C9orf72-negative patients. Heritability estimates were highest in mother-daughter pairings (66.2%; 95% CI 58.5%-73.9%).