Evidence map analysis of influencing factors of type 2 diabetes mellitus in Mendelian randomization study
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摘要:
目的 基于孟德尔随机化(MR)方法，系统梳理2型糖尿病(T2DM)的潜在因果影响因素，构建证据图谱以全面评估现有研究的特征与质量。 方法 计算机检索建库至2024年4月，在中国知网(CNKI)、万方(Wanfang)、PubMed、Web of Science获取T2DM影响因素的MR相关的研究。使用Excel表对纳入的研究的数据进行提取和整理，并按照MR研究的三大假设对纳入的研究进行质量评价，综合应用发文量折线图、影响因素分类三线表及证据图谱，可视化呈现研究特征、暴露-结局关联及方法学应用。 结果 筛选后共纳入152篇文献(含207项MR研究)，总结了9类暴露与T2DM的因果关联。质量评价显示，32.37%(67/207)的研究基本满足了MR研究的三大假设，91.78%(190/207)的研究对象是欧洲人群，亚洲人群研究不足；方法学上，86.95%(180/207)的研究主要采用逆方差加权法(IVW)，75.36%(156/207)的研究应用3种以上MR分析方法；证据图谱提示，BMI、25-羟基维生素D、低出生体重、失眠以及久坐行为等与2型糖尿病的因果关联证据较强。 结论 本研究系统总结了T2DM与影响因素之间的因果关系，截至2024年4月，T2DM的MR研究主要集中在血液指标、生活习惯、疾病等方面，建议加强对于其他方面的研究，尤其以亚洲人群、中国人群为研究对象的MR研究，并制定MR研究的统一质量评价标准，规范MR分析中的分析方法，为开展更高质量的研究提供标准，从而为T2DM的防治提供更准确的科学依据。 Abstract:Objective To systematically identify the potential causal factors of type 2 diabetes mellitus (T2DM) based on the Mendelian randomization (MR) approach, and to construct an evidence map to comprehensively evaluate the characteristics and quality of existing studies. Methods China National Knowledge Infrastructure (CNKI), Wanfang, PubMed, and Web of Science were searched for studies on MR related to T2DM influencing factors from the database establishment to April 2024. Excel was used to extract and organize the data of the included studies, and the quality of the included studies was evaluated according to the three major hypotheses of MR research. The line chart of the number of publications, the three-line table of influencing factors, and the evidence map were comprehensively used to visualize the study characteristics, exposion-outcome association, and methodological application. Results A total of 152 articles (including 207 MR studies) were included after the screening, which summarized the causal association between 9 types of exposures and T2DM. The quality evaluation showed that 32.37%(67/207) of the studies basically met the three major assumptions of MR research, 91.78% (190/207) of the research objects were European population, and there were not enough studies on the Asian population. In terms of methodology, 86.95% (180/207) of the studies mainly used inverse variance weighting (IVW), and 75.36% (156/207) of the studies used more than 3 MR analysis methods. The evidence map suggested that body mass index, 25-hydroxyvitamin D, low birth weight, insomnia, and sedentary behavior had strong evidence of causal association with type 2 diabetes. Conclusion This study systematically summarizes the causal relationship between T2DM and influencing factors. By April 2024, the MR studies of T2DM will mainly focus on blood indicators, living habits, diseases, and other aspects. It is recommended to strengthen research on other aspects, especially MR studies on the Asian population and Chinese population, and formulate unified quality evaluation criteria for MR studies. To standardize the analytical methods of MR analysis and provide a standard for higher quality research, so as to provide a more accurate scientific basis for the prevention and treatment of T2DM. -
Key words:
- Type 2 diabetes /
- Mendelian randomization /
- Evidence map
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图 2 纳入研究不同年份发文量
Figure 2. The number of publications in different years included in the study
图 3 T2DM影响因素的证据图谱
注：气泡图要素包括MR研究数量、暴露类型、质量分级以及暴露与结局的因果关系。通过比较不同暴露与T2DM之间的研究特征差异，直观地展示出因果关联证据。因一项研究可能包含不同的结局指标，所以一项研究可能包含多个气泡，不同气泡颜色代表不同分类的影响因素；气泡大小代表MR研究样本量的数量；横轴表示因果关系的方向，分为呈正相关、负相关、无相关性；纵轴表示MR研究的质量分级，分为高、中、低。
Figure 3. The spectrum of evidence of influencing factors for T2DM
表 1 纳入研究暴露分类及数量
Table 1. Classification and number of exposures included in the study
暴露分类 MR研究数量 暴露分类 MR研究数量 暴露分类 MR研究数量 暴露分类 MR研究数量 血液指标 82 循环胎球蛋白-A 1 肠道菌群 17 脑癌 1 γ-谷氨酰转移酶 4 酪氨酸 1 毛梭菌属 2 胃癌 1 尿酸 3 SMOC1肝素水平 1 肠道微生物系和相关代谢物 1 肺癌 1 载脂蛋白B 3 血浆神经生长调节因子-1 1 罗斯拜瑞氏菌属 1 胰腺癌 1 花生四烯酸 2 血清叶酸浓度 1 链球菌属 1 淋巴白血病 1 亚油酸 2 循环同型半胱氨酸浓度 1 颤螺旋菌属 1 丙型肝炎 1 低血浆脂联素 2 循环鞘脂 1 瘤胃球菌科UCG 003 1 新型冠状病毒 1 性激素结合球蛋白 2 T淋巴细胞亚群 1 瘤胃球菌科UCG 010 1 发育障碍 1 血清胆红素浓度 2 脂联素 1 泽泻属 1 肝脏脂肪 1 单核细胞 2 胰岛β细胞功能 1 葱孢属 1 胰腺体积 1 高密度脂蛋白-C 2 循环叶绿醌浓度 1 黄曲霉菌属 1 骨密度 1 氨基酸 1 循环ALT(谷丙转氨酶)升高 1 嗜血杆菌属 1 生活习惯 24 甘油三酯 1 循环AST(谷草转氨酶)升高 1 梭菌科 1 失眠 4 血管紧张素转换酶抑制剂 1 循环ALP(碱性磷酸酶)升高 1 革兰氏菌科 1 久坐行为 4 α-亚麻酸 1 免疫球蛋白G N-聚糖 1 放线菌属 1 咖啡摄入 3 棕榈油酸 1 内皮素-1 1 假丝酵母菌属 1 吸烟 2 油酸 1 肾上腺髓质素 1 人类牙胶微生物 1 大麻的使用 2 二十碳五烯酸 1 白细胞介素-18 1 疾病 38 体力活动 2 二十二碳五烯酸 1 他汀类药物诱导的胆固醇反应 1 炎症性肠病 3 不吃早餐 1 硬脂酸 1 高密度脂蛋白胆固醇 1 大动脉僵硬 2 乳制品摄入量 1 转化生长因子-α 1 丁酸盐 1 慢性阻塞性肺疾病 2 孤独 1 CX3CL1 1 支链氨基酸多态性 1 乙型肝炎 2 社会孤立 1 HGDNF 1 丙酸 1 类风湿关节炎 1 生鱼油摄入 1 FGF21 1 胰岛素受体 1 多囊卵巢综合征 1 饮茶 1 大颗粒高密度脂蛋白 1 白细胞 1 骨质疏松 1 面条摄入量 1 小颗粒高密度脂蛋白 1 遗传胎球蛋白-A 1 抑郁症 1 微量元素 12 长链n-6多不饱和脂肪酸 1 体重相关 20 注意力缺陷 1 25-羟基维生素D 6 正常甲状腺功能 1 体重指数 8 多动障碍 1 维生素C 2 皮质醇 1 肥胖 5 高血压 1 血清钙 2 2-羟基丁酸 1 低出生体重 4 银屑病 1 砷代谢 1 生长分化因子15 1 臀围 1 神经性厌食症 1 血清铁 1 促甲状腺素水平 1 腰围 1 HDL脂质代谢紊乱 1 基因相关 7 游离甲状腺素 1 腰臀比 1 非酒精性脂肪肝 1 端粒长短 1 甲状腺功能减退 1 文化程度 3 特应性皮炎 1 血液线粒体DNA拷贝数 1 二十碳五烯酸乙酯 1 教育程度 3 牙周炎 1 HACL1遗传变异 1 血糖水平 1 生命体征 4 静脉血栓栓塞 1 RAD 21遗传变异 1 β-胡萝卜素水平 1 收缩压 1 睡眠呼吸暂停综合征 1 ASH1L遗传变异 1 低密度脂蛋白-C 1 心率变异率 1 多发性骨髓瘤 1 GAK遗传变异 1 巨噬细胞移动抑制因子浓度 1 静息心率 1 非霍奇金淋巴瘤 1 影响炎症和基因测量的基因变异 1 脂蛋白A 1 肺功能 1 膀胱癌 1 DNA甲基化 1 去饱和酶活性 1 注：CX3CL1为C-X3-C基序趋化因子配体1(C-X3-C motif chemokine ligand 1), HGDNF为人胶质细胞源性神经营养因子(human glial cell line-derived neurotrophic factor), FGF21为成纤维细胞生长因子21(recombinant human FGF-21 protein)。 
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