Methods for Estimating ALS Heritability Reviewed in New Report

A group of researchers from the King’s College London recently published a new editorial entitled, “Heritability of Amyotrophic Lateral Sclerosis” in the journal JAMA Neurology – the official journal of the American Medical Association, that comments on the heritability estimation results of amyotrophic lateral sclerosis from a previous study by Margaux F. Keller and colleagues in the same journal.

In that study, titled, “Genome-Wide Analysis of the Heritability of Amyotrophic Lateral Sclerosis,” Keller and colleagues reported an estimation of ALS heritability at nearly 21%.  This result was obtained using data from 3 genome-wide association studies, with a total of 1,223 ALS cases and 1,591 controls. The information was provided by the National Center for Biotechnology Information database of genotypes and phenotypes. Moreover, the researchers identified 17 regions of the genome that displayed high heritability estimates, leading to a conclusion that eleven of these regions represent novel candidate regions for ALS risk. To compute genome data, the researchers used a software called GCTA that uses linear mixed models accounting for all single-nucleotide polymorphisms simultaneously.

A previous study conducted by Isabella Fogh and colleagues at King’s College, reported the heritability of sporadic ALS estimation ranging from 20% to 25% across 8 independent cohorts (using an identical estimation method but with a larger sample of 6,100 cases and 7,125 control individuals). The study entitled “ A genome-wide association meta-analysis identifies a novel locus at 17q11.2 associated with sporadic amyotrophic lateral sclerosis”, was published in the journal Human Molecular Genetics. 

Based on the newly-reported findings from Keller and colleagues that achieve similar estimations using similar methods, Isabella Fogh’s research team positively commented in the editorial. However, since it is difficult to address estimation rates in a rare condition such as ALS, the researchers concluded in the editorial that this estimation approach “has been applied to estimates for the heritability of ALS from family data obtained from a research register. For the same range of prevalence, heritability estimated from family data is consistently greater than values for heritability that we have estimated using common variation, indicating that there are potentially rarer variants not captured by commercial genotyping arrays that contribute to the risk for ALS”.