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遗传成瘾风险严重程度(GARS)测试中风险等位基因的统计验证:对74566例病例对照受试者酒精使用障碍(AUD)风险的早期识别

Statistical Validation of Risk Alleles in Genetic Addiction Risk Severity (GARS) Test: Early Identification of Risk for Alcohol Use Disorder (AUD) in 74,566 Case-Control Subjects.

作者信息

Blum Kenneth, Han David, Gupta Ashim, Baron David, Braverman Eric R, Dennen Catherine A, Kazmi Shan, Llanos-Gomez Luis, Badgaiyan Rajendra D, Elman Igor, Thanos Panayotis K, Downs Bill W, Bagchi Debasis, Gondre-Lewis Marjorie C, Gold Mark S, Bowirrat Abdalla

机构信息

Graduate College, Western University Health Sciences, Pomona, CA 91766, USA.

Institute of Psychology, ELTE Eötvös Loránd University, Egyetem tér 1-3, 1053 Budapest, Hungary.

出版信息

J Pers Med. 2022 Aug 26;12(9):1385. doi: 10.3390/jpm12091385.

Abstract

Since 1990, when our laboratory published the association of the DRD2 Taq A1 allele and severe alcoholism in , there has been an explosion of genetic candidate association studies, including GWAS. To develop an accurate test to help identify those at risk for at least Alcohol Use Disorder (AUD), 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 published from 1990 until 2021. This analysis calculated the Hardy-Weinberg Equilibrium of each polymorphism in cases and controls. If available, the Pearson's test or Fisher's exact test was applied to comparisons of the gender, genotype, and allele distribution. The statistical analyses found the OR, 95% CI for OR, and a post-risk for 8% estimation of the population's alcoholism prevalence revealed a significant detection. The OR results showed significance for DRD2, DRD3, DRD4, DAT1, COMT, OPRM1, and 5HTT at 5%. While most of the research related to GARS is derived from our laboratory, we are encouraging more independent research to confirm our findings.

摘要

自1990年我们实验室发表DRD2 Taq A1等位基因与严重酒精中毒的关联以来,包括全基因组关联研究(GWAS)在内的基因候选关联研究如雨后春笋般涌现。为了开发一种准确的测试方法来帮助识别至少有酒精使用障碍(AUD)风险的人群,布卢姆团队开发了遗传成瘾风险严重程度(GARS)测试,该测试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测量的这些风险等位基因的选择,我们对1990年至2021年发表的研究每个多态性与AUD或AUD相关病症关联的研究进行了严格分析。该分析计算了病例组和对照组中每个多态性的哈迪-温伯格平衡。如果可行,应用皮尔逊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%估计的风险后值显示出显著检测结果。OR结果在5%水平上显示DRD2、DRD3、DRD4、DAT1、COMT、OPRM1和5HTT具有显著性。虽然与GARS相关的大部分研究都来自我的实验室,但我们鼓励更多独立研究来证实我们的发现。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f9ac/9505592/bda1804c10f0/jpm-12-01385-g001.jpg

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