Loss-of-function variants inNEK1are associated with an increased risk of sporadic ALS in the Japanese population

Loss-of-function (LoF) variants inNEK1have recently been reported to be associated with amyotrophic lateral sclerosis (ALS). In this study, we investigated the association ofNEK1LoF variants with an increased risk of sporadic ALS (SALS) and the clinical characteristics of patients with SALS carrying LoF variants in a Japanese case series. Whole-exome sequencing analysis was performed for a series of 446 SALS patients in whom pathogenic variants in familial ALS-causative genes have not been identified and 1163 healthy control subjects in our Japanese series. We evaluated LoF variants, defined as nonsense, splice-site disrupting single-nucleotide variants (SNVs), or short insertion/deletion (indel) variants predicted to cause frameshifts inNEK1. We identified sevenNEK1LoF variants in patients with SALS (1.57%), whereas only one was identified in control subjects (0.086%) (P = 0.00073, Fisher's exact test). This finding is consistent with those in recent reports from other regions in the world. In conclusion, we demonstrated thatNEK1LoF variants are also associated with an increased risk of SALS in the Japanese population.

Automated summary

The study discovered that NEK1 LoF variants are associated with an increased risk of SALS in the Japanese population.