Department of Psychiatry, Washington University School of Medicine, St. Louis, Missouri, USA.
Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA.
Transl Behav Med. 2018 Jan 29;8(1):7-17. doi: 10.1093/tbm/ibx060.
The incorporation of genomic information into routine care settings is a burgeoning area for investigation in behavioral medicine. The past decade has witnessed rapid advancements in knowledge of genetic biomarkers associated with smoking behaviors and tobacco-related morbidity and mortality, providing the basis for promising genomic applications in clinical and community settings. We assessed the current state of readiness for implementing genomic applications involving variation in the α5 nicotinic cholinergic receptor subunit gene CHRNA5 and smoking outcomes (behaviors and related diseases) using a process that could be translatable to a wide range of genomic applications in behavioral medicine. We reviewed the scientific literature involving CHRNA5 genetic variation and smoking cessation, and then summarized and synthesized a chain of evidence according to analytic validity, clinical validity, clinical utility, and ethical, legal, and social implications (ACCE), a well-established set of criteria used to evaluate genomic applications. Our review identified at least three specific genomic applications for which implementation may be considered, including the use of CHRNA5 genetic test results for informing disease risk, optimizing smoking cessation treatment, and motivating smoking behavior change. For these genomic applications, we rated analytic validity as convincing, clinical validity as adequate, and clinical utility and ethical, legal, and social implications as inadequate. For clinical genomic applications involving CHRNA5 variation and smoking outcomes, research efforts now need to focus on establishing clinical utility. This approach is compatible with pre-implementation research, which is also needed to accelerate translation, improve innovation design, and understand and refine system processes involved in implementation. This study informs the readiness to incorporate smoking-related genomic applications in real-world settings and facilitates cross-disciplinary collaboration to accelerate the integration of evidence-based genomics in behavioral medicine.
将基因组信息纳入常规护理环境是行为医学中一个新兴的研究领域。在过去的十年中，与吸烟行为以及与烟草相关的发病率和死亡率相关的遗传生物标志物的知识取得了快速进展，为临床和社区环境中具有前景的基因组应用提供了基础。我们使用一种可以转化为行为医学中广泛的基因组应用的过程，评估了涉及α5 烟碱型乙酰胆碱受体亚基基因 CHRNA5 变异和吸烟结局（行为和相关疾病）的基因组应用实施的准备情况。我们回顾了涉及 CHRNA5 遗传变异和戒烟的科学文献，然后根据分析有效性、临床有效性、临床实用性以及伦理、法律和社会影响（ACCE）总结并综合了证据链，这是一套用于评估基因组应用的既定标准。我们的综述确定了至少三个可以考虑实施的特定基因组应用，包括使用 CHRNA5 遗传测试结果来告知疾病风险、优化戒烟治疗以及激发吸烟行为改变。对于这些基因组应用，我们认为分析有效性令人信服，临床有效性足够，而临床实用性以及伦理、法律和社会影响不足。对于涉及 CHRNA5 变异和吸烟结局的临床基因组应用，现在需要集中精力确定临床实用性。这种方法与实施前研究兼容，这也是加速转化、改进创新设计以及理解和改进实施中涉及的系统过程所必需的。本研究为在实际环境中纳入与吸烟相关的基因组应用提供了准备情况，并促进了跨学科合作，以加速行为医学中基于证据的基因组学的整合。
