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

被引:7
作者
Almli, Lynn M. [1 ]
Lori, Adriana [1 ]
Meyers, Jacquelyn L. [2 ]
Shin, Jaemin [3 ]
Fani, Negar [1 ]
Maihofer, Adam X. [4 ,5 ]
Nievergelt, Caroline M. [4 ,5 ]
Smith, Alicia K. [1 ,6 ]
Mercer, Kristina B. [7 ]
Kerley, Kimberly [1 ]
Leveille, Jennifer M. [1 ]
Feng, Hao [7 ]
Abu-Amara, Duna [8 ]
Flory, Janine D. [8 ,9 ]
Yehuda, Rachel [8 ,9 ]
Marmar, Charles R. [8 ]
Baker, Dewleen G. [4 ,5 ,10 ]
Bradley, Bekh [1 ,11 ]
Koenen, Karestan C. [12 ]
Conneely, Karen N. [7 ]
Ressler, Kerry J. [1 ,13 ]
机构
[1] Emory Univ, Dept Psychiat & Behav Sci, Atlanta, GA 30322 USA
[2] Suny Downstate Med Ctr, Dept Psychiat, Brooklyn, NY 11203 USA
[3] Georgia State Univ, Georgia Inst Technol, Ctr Adv Brain Imaging, Atlanta, GA 30303 USA
[4] Univ Calif San Diego, Dept Psychiat, San Diego, CA 92103 USA
[5] Vet Affairs Ctr Excellence Stress & Mental Hlth, San Diego, CA USA
[6] Emory Univ, Dept Gynecol & Obstet, Atlanta, GA 30322 USA
[7] Emory Univ, Dept Human Genet, Atlanta, GA 30322 USA
[8] NYU, Dept Psychiat, Steven & Alexandra Cohen Vet Ctr Posttraumat Stre, 550 1St Ave, New York, NY 10016 USA
[9] MSSM James J Peters Vet Adm Med Ctr, Dept Psychiat, New York, NY USA
[10] VA San Diego Healthcare Syst, Psychiat Serv, San Diego, CA USA
[11] Dept Vet Affairs Med Ctr, Mental Hlth Serv Line, Atlanta, GA USA
[12] Harvard TH Chan Sch Publ Hlth, Dept Epidemiol, Boston, MA USA
[13] Harvard Med Sch, McLean Hosp, Belmont, MA USA
关键词
alcohol consumption; alcohol use disorder; AUDIT; expression QTL; fMRI; genome-wide association study; GENOME-WIDE ASSOCIATION; POSTTRAUMATIC-STRESS-DISORDER; ABUSE SCREENING-TEST; IDENTIFICATION TEST AUDIT; PSYCHOMETRIC PROPERTIES; FUNCTIONAL CONNECTIVITY; EXECUTIVE CONTROL; EUROPEAN-AMERICANS; HAPLOTYPE ANALYSIS; AFRICAN-AMERICANS;
D O I
10.1111/adb.12569
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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=2.61x10(-8) (dominant model), P=7.76x10(-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.
引用
收藏
页码:1145 / 1159
页数:15
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