An estimate of amyotrophic lateral sclerosis heritability using twin data

Ammar Al-Chalabi (1) , Fang Fang (2) , Martha F Hanby (1) , P Nigel Leigh (1) , Christopher E Shaw (1) , Weimin Ye (2) , Fruhling Rijsdijk (1)

1 Institute of Psychiatry
2 Karolinska Institutet [Stockholm]

Causative gene mutations have been identified in about 2% of those with amyotrophic lateral sclerosis (ALS), often, but not always, when there is a strong family history. There is an assumption that there is a genetic component to all ALS, but genome-wide association studies have yet to produce a robustly replicated result. A definitive estimate of ALS heritability is therefore required to determine whether ongoing efforts to find susceptibility genes are worthwhile. We have performed two twin studies, one population and one clinic based. We used structural equation modelling to perform a meta-analysis of data from these studies and an existing twin study, to estimate ALS heritability. We identified 171 twin pairs in which at least one twin had ALS. Five monozygotic twin pairs were concordant affected and 44 discordant. No dizygotic twin pairs were concordant affected and 122 were discordant. The heritability of sporadic ALS was estimated as 0.61 (0.38, 0.78) with the unshared environmental component 0.39 (0.22, 0.62). ALS has high heritability and efforts to find causative genes should continue.

Mots clés: ALS; GENETICS; MOTOR NEURON DISEASE

Ammar Al-Chalabi, Fang Fang, Martha F Hanby, P Nigel Leigh, Christopher E Shaw, et al.. An estimate of amyotrophic lateral sclerosis heritability using twin data. Journal of Neurology, Neurosurgery and Psychiatry, 2010, 81 (12), pp.1324. ⟨10.1136/jnnp.2010.207464⟩. ⟨hal-00578725⟩