This umbrella review investigates which genetic factors are associated with drug-related movement disorders (DRMD), in an attempt to provide a synthesis of published evidence of candidate-gene studies. To identify all relevant meta-analyses, a literature search was performed. Titles and abstracts were screened by two authors and the methodological quality of included meta-analyses was assessed using 'the assessment of multiple systematic reviews' (AMSTAR) critical appraisal checklist. The search yielded 15 meta-analytic studies reporting on genetic variations in 10 genes. DRD3, DRD2, CYP2D6, HTR2A, COMT, HSPG2 and SOD2 genes have variants that may increase the odds of TD. However, these findings do not concur with early genome-wide association studies. Low-power samples are susceptible to 'winner's curse', which was supported by diminishing meta-analytic effects of several genetic variants over time. Furthermore, analyses pertaining to the same genetic variant were difficult to compare due to differences in patient populations, methods used and the choice of studies included in meta-analyses. In conclusion, DRMD is a complex phenotype with multiple genes that impact the probability of onset. More studies with larger samples using other methods than by candidate genes, are essential to developing methods that may predict the probability of DRMD. To achieve this, multiple research groups need to collaborate and a DRMD genetic database needs to be established in order to overcome winner's curse and publication bias, and to allow for stratification by patient characteristics. These endeavours may help the development of a test with clinical value in the prevention and treatment of DRMD.

中文翻译：

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药物相关运动障碍的遗传学，荟萃分析的综合综述。

这篇综述性综述调查了哪些遗传因素与药物相关运动障碍 (DRMD) 相关，试图提供候选基因研究已发表证据的综合。为了确定所有相关的荟萃分析，进行了文献检索。标题和摘要由两位作者筛选，纳入的荟萃分析的方法学质量使用“多重系统评价评估”（AMSTAR）关键评估清单进行评估。搜索产生了 15 项荟萃分析研究，报告了 10 个基因的遗传变异。DRD3、DRD2、CYP2D6、HTR2A、COMT、HSPG2 和 SOD2 基因具有可能增加 TD 几率的变异。然而，这些发现与早期的全基因组关联研究不一致。低功率样本容易受到“赢家诅咒”的影响，随着时间的推移，几种遗传变异的元分析效应逐渐减弱，这一点得到了支持。此外，由于患者人群、使用的方法和荟萃分析中包含的研究选择的差异，难以比较与相同遗传变异有关的分析。总之，DRMD 是一种复杂的表型，具有多个影响发病概率的基因。使用其他方法而不是候选基因对更大样本的更多研究对于开发可以预测 DRMD 概率的方法至关重要。为实现这一目标，需要多个研究小组合作，并且需要建立一个 DRMD 基因数据库，以克服赢家诅咒和发表偏倚，并允许根据患者特征进行分层。