Problematic alcohol use associates with sodium channel and clathrin linker 1 (SCLT1) in trauma ‐exposed populations

We report results from a genome‐wide association study of alcohol consumption and associated problems as measured by the alcohol use disorders identification test (AUDIT) in a trauma‐exposed cohort. Results indicate a genome‐wide significant association between total AUDIT score and rs1433375 [N = 1036, P = 2.61 × 10−8 (dominant model), P = 7.76 × 10−8 (additive model)], an intergenic single‐nucleotide polymorphism located 323 kb upstream of the sodium channel and clathrin linker 1 (SCLT1) at 4q28. rs1433375 was also significant in a meta‐analysis of two similar, but independent, cohorts (N = 1394, P = 0.0004), the Marine Resiliency Study and Systems Biology PTSD Biomarkers Consortium. Functional analysis indicated that rs1433375 was associated with SCLT1 gene expression and cortical‐cerebellar functional connectivity measured via resting state functional magnetic resonance imaging. Together, findings suggest a role for sodium channel regulation and cerebellar functioning in alcohol use behavior. Identifying mechanisms underlying risk for problematic alcohol use in trauma‐exposed populations is critical for future treatment and prevention efforts. Excessive alcohol use is extremely prevalent in the United States, particularly among trauma‐exposed individuals. Our study identifies a novel association between intergenic variant rs1433375 (upstream of SCLT1, a gene associated with the regulation of sodium channel functioning, a putative targ...
Source: Addiction Biology - Category: Addiction Authors: Tags: Original Article Source Type: research