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A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus.

ABSTRACT: Traumatic life experiences are associated with alcohol use problems, an association that is likely to be moderated by genetic predisposition. To understand these interactions, we conducted a gene-by-environment genome-wide interaction study (GEWIS) of alcohol use problems in two independent samples, the Army STARRS (STARRS, N=16?361) and the Yale-Penn (N=8084) cohorts. Because the two cohorts were assessed using different instruments, we derived separate dimensional alcohol misuse scales and applied a proxy-phenotype study design. In African-American subjects, we identified an interaction of PRKG1 rs1729578 with trauma exposure in the STARRS cohort and replicated its interaction with trauma exposure in the Yale-Penn cohort (discovery-replication meta-analysis: z=5.64, P=1.69 × 10-8). PRKG1 encodes cyclic GMP-dependent protein kinase 1, which is involved in learning, memory and circadian rhythm regulation. Considering the loci identified in stage-1 that showed same effect directions in stage-2, the gene ontology (GO) enrichment analysis showed several significant results, including calcium-activated potassium channels (GO:0016286; P=2.30 × 10-5), cognition (GO:0050890; P=1.90 × 10-6), locomotion (GO:0040011; P=6.70 × 10-5) and Stat3 protein regulation (GO:0042517; P=6.4 × 10-5). To our knowledge, this is the largest GEWIS performed in psychiatric genetics, and the first GEWIS examining risk for alcohol misuse. Our results add to a growing body of literature highlighting the dynamic impact of experience on individual genetic risk.

SUBMITTER: Polimanti R

PROVIDER: S-EPMC5589475 | biostudies-literature | 2018 Jan

REPOSITORIES: biostudies-literature

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A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus.

Polimanti R R Kaufman J J Zhao H H Kranzler H R HR Ursano R J RJ Kessler R C RC Gelernter J J Stein M B MB

Molecular psychiatry 20170307 1

Traumatic life experiences are associated with alcohol use problems, an association that is likely to be moderated by genetic predisposition. To understand these interactions, we conducted a gene-by-environment genome-wide interaction study (GEWIS) of alcohol use problems in two independent samples, the Army STARRS (STARRS, N=16 361) and the Yale-Penn (N=8084) cohorts. Because the two cohorts were assessed using different instruments, we derived separate dimensional alcohol misuse scales and app ...[more]

PMID: 28265120

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Project description:BACKGROUND:The American College of Surgeons mandates universal screening for alcohol misuse and delivery of an intervention for those screening positive as a requirement for certification as a level 1 trauma center. Though this requirement has been mandated for over a decade, its implementation has been challenging. Our research team completed an implementation study supporting seven pediatric trauma centers' compliance with the requirement by developing and implementing an institutional alcohol Screening, Brief Intervention and Referral to Treatment (SBIRT) policy for adolescent trauma patients. A mixed-methods approach indicated that SBIRT adoption rates increased at all sites; however, providers' fidelity to the SBIRT intervention was variable, and providers reported a number of barriers to SBIRT implementation. The goal of this study is to conduct a fully powered type III hybrid effectiveness-implementation trial to test the effectiveness of a comprehensive implementation strategy in increasing the implementation of SBIRT for alcohol and other drug use (AOD) in pediatric trauma centers. METHODS:Our implementation strategy is based on the Science to Service Laboratory (SSL), an approach developed by the SAMHSA-funded Addiction Technology Transfer Centers that consists of three core elements (i.e., didactic training + performance feedback + leadership coaching). Utilizing a stepped wedge design, a national cohort of 10 pediatric trauma centers will receive the SSL implementation strategy. At six distinct time points, each of the 10 sites will provide data from 30 electronic medical records (n?=?1800 in total). A subset of adolescents will also report on fidelity of intervention delivery and linkage to care (i.e., continued AOD discussion and/or treatment with a primary care provider) 1 month after hospital discharge. In addition, nurses, social workers, and leaders will report on organizational readiness for implementation at four distinct time points. DISCUSSION:This protocol proposes a unique opportunity to examine whether a comprehensive implementation strategy can improve the fidelity of SBIRT delivery across a national cohort of pediatric trauma centers. With injured adolescents, this could optimize the detection and intervention of AOD use and improve adolescent health. TRIAL REGISTRATION:Clinicaltrials.gov NCT03297060 .

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Dataset Information

A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus.

Publications

A genome-wide gene-by-trauma interaction study of alcohol misuse in two independent cohorts identifies PRKG1 as a risk locus.

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