Blum Kenneth, Han David, Bowirrat Abdalla, Downs Bernard William, Bagchi Debasis, Thanos Panayotis K, Baron David, Braverman Eric R, Dennen Catherine A, Gupta Ashim, Elman Igor, Badgaiyan Rajendra D, Llanos-Gomez Luis, Khalsa Jag, Barh Debmalya, McLaughlin Thomas, Gold Mark S
Division of Addiction Research & Education, Center for Sports, Exercise, and Mental Health, Western University of Health Sciences, Pomona, CA 91766, USA.
Division of Nutrigenomics, The Kenneth Blum Behavioral Neurogenetic Institute, LLC, Austin, TX 78701, USA.
J Pers Med. 2022 Oct 27;12(11):1772. doi: 10.3390/jpm12111772.
Since 1990, when our laboratory published the association of the allele and severe alcoholism in JAMA, there has been an explosion of genetic candidate association studies, including genome-wide association studies (GWAS). To develop an accurate test to help identify those at risk for at least alcohol use disorder (AUD), a subset of reward deficiency syndrome (RDS), Blum's group developed the genetic addiction risk severity (GARS) test, consisting of ten genes and eleven associated risk alleles. In order to statistically validate the selection of these risk alleles measured by GARS, we applied strict analysis to studies that investigated the association of each polymorphism with AUD or AUD-related conditions, including pain and even bariatric surgery, as a predictor of severe vulnerability to unwanted addictive behaviors, published since 1990 until now. This analysis calculated the Hardy-Weinberg Equilibrium of each polymorphism in cases and controls. Pearson's χ test or Fisher's exact test was applied to compare the gender, genotype, and allele distribution if available. The statistical analyses found the OR, 95% CI for OR, and the post risk for 8% estimation of the population's alcoholism prevalence revealed a significant detection. Prior to these results, the United States and European patents on a ten gene panel and eleven risk alleles have been issued. In the face of the new construct of the "preaddiction" model, similar to "prediabetes", the genetic addiction risk analysis might provide one solution missing in the treatment and prevention of the neurological disorder known as RDS.
自1990年我们实验室在《美国医学会杂志》上发表关于该等位基因与严重酒精中毒的关联以来,遗传候选关联研究呈爆炸式增长,包括全基因组关联研究(GWAS)。为开发一种准确的检测方法,以帮助识别至少有酒精使用障碍(AUD)风险的人群(AUD是奖赏缺乏综合征(RDS)的一个子集),布卢姆团队开发了遗传成瘾风险严重程度(GARS)检测,该检测由十个基因和十一个相关风险等位基因组成。为了从统计学上验证通过GARS检测所测量的这些风险等位基因的选择,我们对1990年至今发表的研究进行了严格分析,这些研究调查了每种多态性与AUD或与AUD相关病症(包括疼痛甚至减肥手术)之间的关联,以此作为对不良成瘾行为严重易感性的预测指标。该分析计算了病例组和对照组中每种多态性的哈迪-温伯格平衡。若有可用数据,应用皮尔逊卡方检验或费舍尔精确检验来比较性别、基因型和等位基因分布。统计分析发现,比值比(OR)、OR的95%置信区间以及对人群酒精中毒患病率8%估计的后验风险显示出显著检测结果。在得出这些结果之前,关于一个包含十个基因的基因组合和十一个风险等位基因的美国和欧洲专利已经获批。面对类似于“糖尿病前期”的“成瘾前期”模型的新架构,遗传成瘾风险分析可能为治疗和预防被称为RDS的神经疾病提供一种缺失的解决方案。