How much of the missing heritability of ALS is hidden in known ALS genes?

Further research of rare variants in ALS genes is needed to guide diagnosis and counseling of patients

Over the last decade, our knowledge about the heritability of Amyotrophic Lateral Sclerosis  (ALS) has greatly improved. More than 25 genes have been associated with ALS.1 Some gene mutations segregate with high penetrance in people with familial ALS, some genetic variants have a lower penetrance or merely act as ALS risk alleles. With all of these genes roughly 40%–80% of familial ALS, but also 5%–15% of sporadic ALS can be explained. Indeed, in patients with sporadic ALS, a genetic component is also present: the estimated heritability of sporadic ALS is about 60%.2 This suggests that the genetic architecture of ALS is complex and consists of a mixture of gene mutations that differ in noxiousness and in frequency. At the same time, it is clear that there is considerable missing heritability....

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader https://ift.tt/2Hfnzmd