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To the Editor We read with interest the article by Keller et al1 titled “Genome-Wide Analysis of the Heritability of Amyotrophic Lateral Sclerosis,” in which the contribution of common variation to the heritability (h2) of amyotrophic lateral sclerosis (ALS) was estimated to be 21%. The authors used the popular GCTA software, which uses a linear mixed model accounting for all single-nucleotide polymorphisms simultaneously, with imputed genotype data for 1223 cases and 1591 control individuals. They estimated heritability under the assumption of a disease prevalence of 10 of 100 000 person-years. We previously reported the heritability of sporadic ALS using identical methods and a larger sample of 6100 cases and 7125 control individuals.2 The prevalence of a rare disease, such as ALS, is difficult to estimate and ALS prevalence could be underestimated in populations where life expectancy is progressively increasing. Thus, we estimated heritability over a range of prevalences (see the Results section of our article2) and presented the results in Supplementary Figure S5 of our publication.2
Fogh I, Al-Chalabi A, Powell J. Heritability of Amyotrophic Lateral Sclerosis. JAMA Neurol. 2014;71(12):1579-1580. doi:10.1001/jamaneurol.2014.3493