Homozygosity for the C allele at <i>UNC13A</i> rs12608932 seems to compromise cognition in ALS independently of the cognitive domains

The common single nucleotide polymorphism (SNP) rs12608932 located at a cryptic splice in the <i>UNC13A</i> gene has been reported to modify the clinical phenotype of ALS, but it is unclear whether homozygosity for the C-allele at <i>UNC13A</i> rs12608932 modifies specific domains of cognition in ALS. We analyzed retrospective data from a German cohort and found that the proportion of cognitively or behaviorally impaired patients was higher in the high-risk group of homozygous C-allele carriers. Patients with C/C alleles had lower scores than controls on verbal fluency, executive functioning, and delayed memory recall, but did not differ significantly from other ALS genotypes. Furthermore, informant ratings suggested higher disinhibition in the C/C carriers. These findings indicate that the C/C risk variant of <i>UNC13A</i> rs12608932 may contribute to general cognitive vulnerability rather than domain-specific deficit.