Problematic alcohol use associates with sodium channel and clathrin linker 1 (SCLT1) in trauma‐exposed populations
Abstract
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.
Document Details
- Document Type
- Pub Defense Publication
- Publication Date
- Oct 30, 2017
- Source ID
- 10.1111/adb.12569
Entities
People
- Adam X. Maihofer
- Adriana Lori
- Alicia K. Smith
- Bekh Bradley
- Caroline M Nievergelt
- Charles R. Marmar
- Dewleen G Baker
- Duna Abu‐amara
- Feng Hao
- Jacquelyn L. Meyers
- Jaemin Shin
- Janine D. Flory
- Jennifer M. Leveille
- Karen N. Conneely
- Karestan C. Koenen
- Kerry J. Ressler
- Kimberly Kerley
- Kristina B. Mercer
- Lynn M. Almli
- Negar Fani
- Rachel Yehuda
Organizations
- Emory University
- Georgia State University
- Harvard Medical School
- Harvard University
- Howard Hughes Medical Institute
- National Center for Research Resources
- National Institute of Mental Health
- National Institute on Drug Abuse
- New York University
- State University of New York
- United States Department of Defense
- United States Department of Veterans Affairs
- University of California, San Diego
- VA San Diego Healthcare System