Lifetime risk and heritability of amyotrophic lateral sclerosis


  • Priscilla Lynch
  • Univadis Medical News
El acceso al contenido completo es sólo para profesionales sanitarios registrados. El acceso al contenido completo es sólo para profesionales sanitarios registrados.

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%).