rs12608932 is a risk SNP for amyotrophic lateral sclerosis (ALS)33 located in an intronic region of UNC13A. This has led some to consider UNC13A as a candidate gene in ALS pathology30. We find that rs12608932 is a significant exon-level cis-eQTL for KCNN1 in frontal cortex only (P = 7.11 × 10−7 for expression ID 3824686; Fig. 7b). Both UNC13A and KCNN1 are highly expressed in healthy human brain. UNC13A is implicated in the regulation of neurotransmitter release34,35, and KCNN1 (a voltage-independent calcium-activated potassium channel gene) is implicated in the regulation of neuronal excitability by contributing to the slow component of synaptic after hyperpolarization36. Thus, both genes represent plausible a priori functional candidates, but our region-specific eQTL data weigh in in favor of KCNN1.
