Global Health Research Center, Duke Kunshan University, No. 8 Duke Avenue, Kunshan, Jiangsu, 215316, China.
Department of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, 615 North Wolfe Street, Baltimore, MD, 21205, USA.
Syst Rev. 2022 Sep 2;11(1):185. doi: 10.1186/s13643-022-02050-y.
The mutant allele (*2) of aldehyde dehydrogenase type 2 (ALDH2) caused by a single nucleotide variant (rs671) inhibits enzymatic activity and is associated with multiple diseases. In recent years, an explosive number of original studies and meta-analyses have been conducted to examine the associations of ALDH2 rs671 polymorphism with diseases. Due to conflicting results, the overall associations of ALDH2 rs671 polymorphism and multiple diseases remain unclear.
A quantitative umbrella review will be conducted on meta-analyses of genetic association studies to examine the pleiotropic effects of ALDH2 rs671, mainly including cardio-cerebral vascular disease, diabetes mellitus, cancer, neurodegenerative disease, and alcohol-induced medical disease. A search of relevant literature according to comprehensive search strategies will be performed on studies published before July 1st, 2022 in PubMed, MEDLINE Ovid, Embase, Cochrane Database of Systematic Reviews, and Web of Science. Study selection, data extraction, methodology quality assessment, and strength of evidence assessment will be conducted by two reviewers independently and in duplicate. Included meta-analyses will be grouped by outcomes. Data conflicts and overlap between meta-analyses will be managed through updated standardized and customized methods including the calculation of CCA for study selection reference, application of Doi plots to assess small-study effects and others. Evidence from included meta-analyses will be quantitatively synthesized by overlap-corrected analyses and meta-analysis using primary studies.
This umbrella review is expected to generate systematic evidence on the association between ALDH2 rs671 and diseases. Specific approaches were developed to address key challenges in conducting an umbrella review, including assessment tools of methodology and evidence quality of meta-analyses, methods to manage overlap between meta-analyses, a "stop-light" plot to summarize key findings. These approaches provide applicable methods for future umbrella reviews of meta-analyses on genetic association studies.
CRD42021223812.
乙醛脱氢酶 2 型（ALDH2）的突变等位基因（*2）由单个核苷酸变异（rs671）引起，抑制酶活性，并与多种疾病相关。近年来，大量的原始研究和荟萃分析已经进行，以研究 ALDH2 rs671 多态性与疾病的关联。由于结果相互矛盾，ALDH2 rs671 多态性与多种疾病的总体关联仍不清楚。
我们将对遗传关联研究的荟萃分析进行定量伞式综述，以检查 ALDH2 rs671 的多效性效应，主要包括心脑血管疾病、糖尿病、癌症、神经退行性疾病和酒精引起的医学疾病。根据全面的搜索策略，我们将在 2022 年 7 月 1 日之前在 PubMed、MEDLINE Ovid、Embase、Cochrane 系统评价数据库和 Web of Science 上搜索相关文献。两名评审员将独立地、重复地进行研究选择、数据提取、方法学质量评估和证据强度评估。纳入的荟萃分析将按结果进行分组。通过更新的标准化和定制方法（包括计算研究选择参考的 CCA、应用 Doi 图评估小样本研究效应等）来管理荟萃分析之间的数据冲突和重叠。通过重叠校正分析和使用原始研究的荟萃分析对纳入的荟萃分析中的证据进行定量综合。
本伞式综述预计将产生关于 ALDH2 rs671 与疾病之间关联的系统证据。为解决进行伞式综述的关键挑战，制定了具体的方法，包括荟萃分析方法学和证据质量评估工具、管理荟萃分析之间重叠的方法、总结关键发现的“红绿灯”图。这些方法为未来关于遗传关联研究的荟萃分析的伞式综述提供了适用的方法。
CRD42021223812。
