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Open Access Publications from the University of California

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

  • Author(s): Almli, LM
  • Lori, A
  • Meyers, JL
  • Shin, J
  • Fani, N
  • Maihofer, AX
  • Nievergelt, CM
  • Smith, AK
  • Mercer, KB
  • Kerley, K
  • Leveille, JM
  • Feng, H
  • Abu-Amara, D
  • Flory, JD
  • Yehuda, R
  • Marmar, CR
  • Baker, DG
  • Bradley, B
  • Koenen, KC
  • Conneely, KN
  • Ressler, KJ
  • et al.

Published Web Location Commons 'BY-NC-ND' version 4.0 license

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.

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