- Almli, Lynn M;
- Lori, Adriana;
- Meyers, Jacquelyn L;
- Shin, Jaemin;
- Fani, Negar;
- Maihofer, Adam X;
- Nievergelt, Caroline M;
- Smith, Alicia K;
- Mercer, Kristina B;
- Kerley, Kimberly;
- Leveille, Jennifer M;
- Feng, Hao;
- Abu‐Amara, Duna;
- Flory, Janine D;
- Yehuda, Rachel;
- Marmar, Charles R;
- Baker, Dewleen G;
- Bradley, Bekh;
- Koenen, Karestan C;
- Conneely, Karen N;
- Ressler, Kerry J
Excessive alcohol use is extremely prevalent in the United States, particularly among trauma-exposed individuals. While several studies have examined genetic influences on alcohol use and related problems, this has not been studied in the context of 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.