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冰毒使用障碍的遗传学:基因关联研究的系统综述和荟萃分析。

Genetics of methamphetamine use disorder: A systematic review and meta-analyses of gene association studies.

机构信息

Mental Health Theme, The Florey Institute of Neuroscience and Mental Health, Parkville, VIC, 3052, Australia; Florey Department of Neuroscience and Mental Health, University of Melbourne, Parkville, VIC, 3052, Australia.

Nash Family Department of Neuroscience, Friedman Brain Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.

出版信息

Neurosci Biobehav Rev. 2021 Jan;120:48-74. doi: 10.1016/j.neubiorev.2020.11.001. Epub 2020 Nov 17.

Abstract

Genetic susceptibility to methamphetamine use disorder is poorly understood. No twin or adequately powered genome-wide association studies (GWASs) have been conducted. However, there are a large number of hypothesis-driven candidate gene association studies, which were systematically reviewed herein. Seventy-six studies were identified, investigating markers of 75 different genes. Allele frequencies, odds ratios, 95 % confidence intervals and power were calculated. Risk of bias was also assessed as a quality measure. Meta-analyses were conducted for gene markers if three or more studies were available. Eleven markers from adequately powered studies were significantly associated with methamphetamine use disorder, with Fatty Acid Amide Hydrolase (FAAH) and Brain Derived Neurotrophic Factor (BDNF) representing promising targets. Limitations of these studies include unclear rationale for candidate gene selection, low power and high risk of bias. Future research should include replications to enable more meta-analyses, well-powered GWASs or whole exome or genome sequencing, as well as twin and family studies to further complement the findings of this review to uncover genetic contributions toward methamphetamine use disorder.

摘要

遗传易感性对冰毒使用障碍的影响尚不清楚。尚未进行双胞胎或充分有力的全基因组关联研究(GWAS)。然而,有大量的假设驱动的候选基因关联研究,本文对其进行了系统综述。确定了 76 项研究,调查了 75 个不同基因的标记物。计算了等位基因频率、优势比、95%置信区间和功效。还将偏倚风险评估作为质量指标。如果有三个或更多研究,则对基因标记物进行荟萃分析。11 个来自有力研究的标记物与冰毒使用障碍显著相关,脂肪酸酰胺水解酶(FAAH)和脑源性神经营养因子(BDNF)是有前途的靶点。这些研究的局限性包括候选基因选择的理由不明确、功效低和偏倚风险高。未来的研究应包括重复研究,以进行更多的荟萃分析、有力的 GWAS 或全外显子或全基因组测序,以及双胞胎和家庭研究,以进一步补充本综述的发现,揭示遗传因素对冰毒使用障碍的影响。

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