
Chinese General Practice ›› 2025, Vol. 28 ›› Issue (21): 2625-2634.DOI: 10.12114/j.issn.1007-9572.2023.0641
Special Issue: 内分泌代谢性疾病最新文章合辑; 肥胖最新文章合辑
• Original Research • Previous Articles Next Articles
Received:2024-04-27
Revised:2024-09-05
Published:2025-07-20
Online:2025-06-05
Contact:
KONG Danli, DING Yuanlin, YU Haibing
通讯作者:
孔丹莉, 丁元林, 于海兵
作者简介:作者贡献:
王爽负责研究的构思与设计、研究的实施;王爽、吴树法、令垚负责论文撰写;王爽、谭茜蔚负责数据整理与分析;曹汝岱、曾慧婷进行图、表绘制与优化;孔丹莉、丁元林、于海兵负责文章的修订,质量控制与审查,对文章整体负责。
基金资助:CLC Number:
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URL: https://www.chinagp.net/EN/10.12114/j.issn.1007-9572.2023.0641
| 研究性状 | PubMed ID/数据来源 | 样本量(例) | 可用SNP位点数量(个) |
|---|---|---|---|
| 暴露因素 | |||
| BMI | 30239722 | 806 834 | 312 |
| WHR | 697 734 | 209 | |
| 中介因素 | |||
| 非脂质代谢物 | 27005778 | 12 134~24 923 | 155 |
| 结局 | |||
| DR | FinnGen | 5 988/314 042(实验/对照) | — |
| PDR | 2 222/314 042(实验/对照) | — | |
| NPDR | 3 446/314 042(实验/对照) | — |
Table 1 General information of GWAS for traits included in the study
| 研究性状 | PubMed ID/数据来源 | 样本量(例) | 可用SNP位点数量(个) |
|---|---|---|---|
| 暴露因素 | |||
| BMI | 30239722 | 806 834 | 312 |
| WHR | 697 734 | 209 | |
| 中介因素 | |||
| 非脂质代谢物 | 27005778 | 12 134~24 923 | 155 |
| 结局 | |||
| DR | FinnGen | 5 988/314 042(实验/对照) | — |
| PDR | 2 222/314 042(实验/对照) | — | |
| NPDR | 3 446/314 042(实验/对照) | — |
| 暴露因素 | 结局 | 分析方法 | OR(95%CI) | SE | P值 |
|---|---|---|---|---|---|
| BMI | DR | IVW | 1.78(1.51~2.09) | 0.08 | 5.3E-12 |
| weighted median | 2.00(1.57~2.54) | 0.12 | 1.6E-08 | ||
| MR Egger回归法 | 2.23(1.50~3.31) | 0.20 | 9.2E-05 | ||
| weighted mode | 2.23(1.35~3.68) | 0.26 | 1.9E-03 | ||
| MR RAPS | 1.76(1.54~2.02) | 0.07 | 2.2E-16 | ||
| WHR | IVW | 1.91(1.57~2.33) | 0.10 | 1.3E-10 | |
| weighted median | 1.72(1.30~2.26) | 0.14 | 1.2E-04 | ||
| MR Egger回归法 | 1.30(0.78~2.15) | 0.26 | 0.315 | ||
| weighted mode | 1.55(0.98~2.46) | 0.24 | 0.065 | ||
| MR RAPS | 1.93(1.63~2.29) | 0.09 | 2.2E-14 | ||
| BMI | PDR | IVW | 1.30(1.14~1.47) | 0.06 | 5.7E-05 |
| weighted median | 1.13(0.89~1.43) | 0.12 | 0.308 | ||
| MR Egger回归法 | 1.40(1.03~1.90) | 0.16 | 0.034 | ||
| weighted mode | 1.00(0.71~1.40) | 0.17 | 0.978 | ||
| MR RAPS | 1.30(1.16~1.46) | 0.06 | 7.5E-06 | ||
| WHR | IVW | 1.51(1.30~1.76) | 0.08 | 8.1E-08 | |
| weighted median | 1.66(1.29~2.13) | 0.13 | 6.9E-05 | ||
| MR Egger回归法 | 1.53(1.04~2.26) | 0.20 | 0.034 | ||
| weighted mode | 1.67(1.20~2.33) | 0.17 | 2.7E-03 | ||
| MR RAPS | 1.49(1.29~1.72) | 0.07 | 4.2E-08 | ||
| BMI | NPDR | IVW | 1.81(1.52~2.17) | 0.09 | 9.4E-11 |
| weighted median | 2.38(1.69~3.36) | 0.18 | 7.3E-07 | ||
| MR Egger回归法 | 2.12(1.34~3.38) | 0.24 | 1.6E-03 | ||
| weighted mode | 2.46(1.49~4.08) | 0.26 | 5.3E-04 | ||
| MR RAPS | 1.80(1.51~2.15) | 0.09 | 9.5E-11 | ||
| WHR | IVW | 1.78(1.40~2.27) | 0.12 | 2.6E-06 | |
| weighted median | 1.44(0.99~2.10) | 0.19 | 0.060 | ||
| MR Egger回归法 | 1.29(0.69~2.39) | 0.32 | 0.426 | ||
| weighted mode | 1.30(0.68~2.49) | 0.33 | 0.435 | ||
| MR RAPS | 1.76(1.41~2.20) | 0.11 | 5.2E-07 |
Table 2 MR analysis results of impact of BMI and WHR on diabetic retinopathy
| 暴露因素 | 结局 | 分析方法 | OR(95%CI) | SE | P值 |
|---|---|---|---|---|---|
| BMI | DR | IVW | 1.78(1.51~2.09) | 0.08 | 5.3E-12 |
| weighted median | 2.00(1.57~2.54) | 0.12 | 1.6E-08 | ||
| MR Egger回归法 | 2.23(1.50~3.31) | 0.20 | 9.2E-05 | ||
| weighted mode | 2.23(1.35~3.68) | 0.26 | 1.9E-03 | ||
| MR RAPS | 1.76(1.54~2.02) | 0.07 | 2.2E-16 | ||
| WHR | IVW | 1.91(1.57~2.33) | 0.10 | 1.3E-10 | |
| weighted median | 1.72(1.30~2.26) | 0.14 | 1.2E-04 | ||
| MR Egger回归法 | 1.30(0.78~2.15) | 0.26 | 0.315 | ||
| weighted mode | 1.55(0.98~2.46) | 0.24 | 0.065 | ||
| MR RAPS | 1.93(1.63~2.29) | 0.09 | 2.2E-14 | ||
| BMI | PDR | IVW | 1.30(1.14~1.47) | 0.06 | 5.7E-05 |
| weighted median | 1.13(0.89~1.43) | 0.12 | 0.308 | ||
| MR Egger回归法 | 1.40(1.03~1.90) | 0.16 | 0.034 | ||
| weighted mode | 1.00(0.71~1.40) | 0.17 | 0.978 | ||
| MR RAPS | 1.30(1.16~1.46) | 0.06 | 7.5E-06 | ||
| WHR | IVW | 1.51(1.30~1.76) | 0.08 | 8.1E-08 | |
| weighted median | 1.66(1.29~2.13) | 0.13 | 6.9E-05 | ||
| MR Egger回归法 | 1.53(1.04~2.26) | 0.20 | 0.034 | ||
| weighted mode | 1.67(1.20~2.33) | 0.17 | 2.7E-03 | ||
| MR RAPS | 1.49(1.29~1.72) | 0.07 | 4.2E-08 | ||
| BMI | NPDR | IVW | 1.81(1.52~2.17) | 0.09 | 9.4E-11 |
| weighted median | 2.38(1.69~3.36) | 0.18 | 7.3E-07 | ||
| MR Egger回归法 | 2.12(1.34~3.38) | 0.24 | 1.6E-03 | ||
| weighted mode | 2.46(1.49~4.08) | 0.26 | 5.3E-04 | ||
| MR RAPS | 1.80(1.51~2.15) | 0.09 | 9.5E-11 | ||
| WHR | IVW | 1.78(1.40~2.27) | 0.12 | 2.6E-06 | |
| weighted median | 1.44(0.99~2.10) | 0.19 | 0.060 | ||
| MR Egger回归法 | 1.29(0.69~2.39) | 0.32 | 0.426 | ||
| weighted mode | 1.30(0.68~2.49) | 0.33 | 0.435 | ||
| MR RAPS | 1.76(1.41~2.20) | 0.11 | 5.2E-07 |
| 暴露因素 | 结局 | Cochran's Q检验 | MR Egger截距法 | MR PRESSO法 | |||
|---|---|---|---|---|---|---|---|
| Q值 | P值 | 截距 | P值 | RSSobsa | P值 | ||
| BMI | DR | 410.08 | <0.001 | -0.004 | 0.220 | 413.54 | <0.001 |
| PDR | 343.94 | 0.018 | -0.002 | 0.340 | 347.08 | 0.017 | |
| NPDR | 325.97 | 0.083 | -0.003 | 0.468 | 328.23 | 0.088 | |
| WHR | DR | 264.93 | <0.001 | 0.007 | 0.104 | 268.55 | <0.001 |
| PDR | 217.56 | 0.128 | 0.003 | 0.947 | 219.72 | 0.132 | |
| NPDR | 231.17 | 0.039 | 0.006 | 0.264 | 238.89 | 0.050 | |
Table 3 Heterogeneity and pleiotropy test for MR analysis results of impact of BMI and WHR on diabetic retinopathy
| 暴露因素 | 结局 | Cochran's Q检验 | MR Egger截距法 | MR PRESSO法 | |||
|---|---|---|---|---|---|---|---|
| Q值 | P值 | 截距 | P值 | RSSobsa | P值 | ||
| BMI | DR | 410.08 | <0.001 | -0.004 | 0.220 | 413.54 | <0.001 |
| PDR | 343.94 | 0.018 | -0.002 | 0.340 | 347.08 | 0.017 | |
| NPDR | 325.97 | 0.083 | -0.003 | 0.468 | 328.23 | 0.088 | |
| WHR | DR | 264.93 | <0.001 | 0.007 | 0.104 | 268.55 | <0.001 |
| PDR | 217.56 | 0.128 | 0.003 | 0.947 | 219.72 | 0.132 | |
| NPDR | 231.17 | 0.039 | 0.006 | 0.264 | 238.89 | 0.050 | |
| 暴露因素 | 结局 | MR分析 | OR(95%CI) | P值 |
|---|---|---|---|---|
| BMI | DR | 原始值 | 1.78(1.51~2.09) | 3.3E-11 |
| 校正值 | 1.81(1.55~2.12) | 1.4E-12 | ||
| PDR | 原始值 | 1.30(1.14~1.47) | 7.3E-05 | |
| 校正值 | NA | NA | ||
| WHR | DR | 原始值 | 1.91(1.57~2.33) | 9.8E-10 |
| 校正值 | 1.92(1.59~2.32) | 1.6E-10 |
Table 4 Corrected MR analysis results of impact of BMI and WHR on diabetic retinopathy by MR PRESSO
| 暴露因素 | 结局 | MR分析 | OR(95%CI) | P值 |
|---|---|---|---|---|
| BMI | DR | 原始值 | 1.78(1.51~2.09) | 3.3E-11 |
| 校正值 | 1.81(1.55~2.12) | 1.4E-12 | ||
| PDR | 原始值 | 1.30(1.14~1.47) | 7.3E-05 | |
| 校正值 | NA | NA | ||
| WHR | DR | 原始值 | 1.91(1.57~2.33) | 9.8E-10 |
| 校正值 | 1.92(1.59~2.32) | 1.6E-10 |
| 暴露因素 | 结局 | 分析方法 | OR(95%CI) | SE | P值 |
|---|---|---|---|---|---|
| 氨基酸 | |||||
| 异亮氨酸 | DR | Wald ratio | 0.62(0.40~0.98) | 0.23 | 0.039 |
| 蛋白质 | |||||
| 白蛋白 | DR | IVW | 0.65(0.49~0.86) | 0.14 | 0.002 |
| weighted median | 0.63(0.50~0.87) | 0.16 | 0.005 | ||
| MR Egger回归法 | 0.59(0.21~1.66) | 0.53 | 0.499 | ||
| weighted mode | 0.63(0.43~0.92) | 0.20 | 0.011 | ||
| MR RAPS | 0.65(0.49~0.87) | 0.15 | 0.004 | ||
| PDR | IVW | 0.66(0.53~0.83) | 0.12 | <0.001 | |
| weighted median | 0.70(0.53~0.93) | 0.14 | 0.013 | ||
| MR Egger回归法 | 0.41(0.18~0.97) | 0.43 | 0.291 | ||
| weighted mode | 0.76(0.53~1.10) | 0.19 | 0.287 | ||
| MR RAPS | 0.66(0.52~0.85) | 0.12 | <0.001 | ||
| NPDR | IVW | 0.70(0.48~0.99) | 0.18 | 0.049 | |
| weighted median | 0.76(0.49~1.18) | 0.23 | 0.220 | ||
| MR Egger回归法 | 1.07(0.27~4.16) | 0.70 | 0.942 | ||
| weighted mode | 0.78(0.48~1.27) | 0.25 | 0.417 | ||
| MR RAPS | 0.69(0.48~1.01) | 0.19 | 0.057 | ||
| 糖蛋白 | DR | IVW | 0.92(0.87~0.97) | 0.03 | 0.002 |
| weighted median | 0.93(0.87~1.01) | 0.04 | 0.076 | ||
| MR Egger回归法 | 0.93(0.84~1.02) | 0.05 | 0.129 | ||
| weighted mode | 0.94(0.87~1.02) | 0.04 | 0.149 | ||
| MR RAPS | 0.92(0.87~0.97) | 0.03 | 0.003 | ||
| NPDR | IVW | 0.92(0.85~0.98) | 0.04 | 0.023 | |
| weighted median | 0.93(0.84~1.03) | 0.05 | 0.142 | ||
| MR Egger回归法 | 0.96(0.85~1.09) | 0.06 | 0.522 | ||
| weighted mode | 0.92(0.84~1.02) | 0.05 | 0.137 | ||
| MR RAPS | 0.92(0.85~0.99) | 0.04 | 0.024 | ||
| 碳水化合物 | |||||
| 丙酮酸 | DR | Wald ratio | 0.60(0.38~0.97) | 0.24 | 0.039 |
| 代谢物比例 | |||||
| 双烯基与双键的比率 | DR | IVW | 0.93(0.86~0.99) | 0.03 | 0.048 |
| weighted median | 0.96(0.88~1.05) | 0.05 | 0.357 | ||
| MR Egger回归法 | 0.94(0.81~1.09) | 0.07 | 0.434 | ||
| weighted mode | 0.96(0.88~1.05) | 0.04 | 0.391 | ||
| MR RAPS | 0.93(0.86~0.99) | 0.04 | 0.049 |
Table 5 MR analysis results of impact of nonlipid metabolites on diabetic retinopathy
| 暴露因素 | 结局 | 分析方法 | OR(95%CI) | SE | P值 |
|---|---|---|---|---|---|
| 氨基酸 | |||||
| 异亮氨酸 | DR | Wald ratio | 0.62(0.40~0.98) | 0.23 | 0.039 |
| 蛋白质 | |||||
| 白蛋白 | DR | IVW | 0.65(0.49~0.86) | 0.14 | 0.002 |
| weighted median | 0.63(0.50~0.87) | 0.16 | 0.005 | ||
| MR Egger回归法 | 0.59(0.21~1.66) | 0.53 | 0.499 | ||
| weighted mode | 0.63(0.43~0.92) | 0.20 | 0.011 | ||
| MR RAPS | 0.65(0.49~0.87) | 0.15 | 0.004 | ||
| PDR | IVW | 0.66(0.53~0.83) | 0.12 | <0.001 | |
| weighted median | 0.70(0.53~0.93) | 0.14 | 0.013 | ||
| MR Egger回归法 | 0.41(0.18~0.97) | 0.43 | 0.291 | ||
| weighted mode | 0.76(0.53~1.10) | 0.19 | 0.287 | ||
| MR RAPS | 0.66(0.52~0.85) | 0.12 | <0.001 | ||
| NPDR | IVW | 0.70(0.48~0.99) | 0.18 | 0.049 | |
| weighted median | 0.76(0.49~1.18) | 0.23 | 0.220 | ||
| MR Egger回归法 | 1.07(0.27~4.16) | 0.70 | 0.942 | ||
| weighted mode | 0.78(0.48~1.27) | 0.25 | 0.417 | ||
| MR RAPS | 0.69(0.48~1.01) | 0.19 | 0.057 | ||
| 糖蛋白 | DR | IVW | 0.92(0.87~0.97) | 0.03 | 0.002 |
| weighted median | 0.93(0.87~1.01) | 0.04 | 0.076 | ||
| MR Egger回归法 | 0.93(0.84~1.02) | 0.05 | 0.129 | ||
| weighted mode | 0.94(0.87~1.02) | 0.04 | 0.149 | ||
| MR RAPS | 0.92(0.87~0.97) | 0.03 | 0.003 | ||
| NPDR | IVW | 0.92(0.85~0.98) | 0.04 | 0.023 | |
| weighted median | 0.93(0.84~1.03) | 0.05 | 0.142 | ||
| MR Egger回归法 | 0.96(0.85~1.09) | 0.06 | 0.522 | ||
| weighted mode | 0.92(0.84~1.02) | 0.05 | 0.137 | ||
| MR RAPS | 0.92(0.85~0.99) | 0.04 | 0.024 | ||
| 碳水化合物 | |||||
| 丙酮酸 | DR | Wald ratio | 0.60(0.38~0.97) | 0.24 | 0.039 |
| 代谢物比例 | |||||
| 双烯基与双键的比率 | DR | IVW | 0.93(0.86~0.99) | 0.03 | 0.048 |
| weighted median | 0.96(0.88~1.05) | 0.05 | 0.357 | ||
| MR Egger回归法 | 0.94(0.81~1.09) | 0.07 | 0.434 | ||
| weighted mode | 0.96(0.88~1.05) | 0.04 | 0.391 | ||
| MR RAPS | 0.93(0.86~0.99) | 0.04 | 0.049 |
| 暴露因素 | 结局 | Cochran's Q检验 | MR Egger截距法 | MR PRESSO法 | |||
|---|---|---|---|---|---|---|---|
| Q值 | P值 | 截距 | P值 | RSSobs | P值 | ||
| 氨基酸 | |||||||
| 异亮氨酸 | DR | — | — | — | — | — | — |
| PDR | — | — | — | — | — | — | |
| NPDR | — | — | — | — | — | — | |
| 缬氨酸 | DR | 2.60 | 0.458 | -0.092 | 0.255 | 4.88 | 0.508 |
| PDR | 0.62 | 0.891 | -0.021 | 0.718 | 0.87 | 0.921 | |
| NPDR | 3.62 | 0.306 | -0.123 | 0.250 | 5.68 | 0.416 | |
| 组氨酸 | DR | 6.59 | 0.159 | 0.050 | 0.487 | 10.01 | 0.210 |
| PDR | 2.69 | 0.611 | -0.011 | 0.793 | 4.26 | 0.620 | |
| NPDR | 2.76 | 0.599 | 0.002 | 0.978 | 4.53 | 0.600 | |
| 肌氨酸 | DR | 1.82 | 0.769 | -0.019 | 0.741 | 3.12 | 0.757 |
| PDR | 2.71 | 0.608 | -0.005 | 0.915 | 4.40 | 0.616 | |
| NPDR | 2.43 | 0.657 | -0.062 | 0.426 | 3.64 | 0.686 | |
| 酪氨酸 | DR | 5.39 | 0.146 | 0.052 | 0.254 | 9.91 | 0.238 |
| PDR | 4.62 | 0.202 | 0.040 | 0.264 | 7.72 | 0.296 | |
| NPDR | 1.84 | 0.607 | 0.028 | 0.546 | 3.05 | 0.656 | |
| 谷氨酰胺 | DR | 8.83 | 0.066 | 0.050 | 0.092 | 27.08 | 0.295 |
| PDR | 2.96 | 0.564 | 0.010 | 0.594 | 4.56 | 0.646 | |
| NPDR | 2.59 | 0.629 | 0.021 | 0.482 | 4.45 | 0.670 | |
| 苯丙氨酸 | DR | 4.60 | 0.100 | -0.045 | 0.569 | — | — |
| PDR | 4.98 | 0.083 | -0.057 | 0.293 | — | — | |
| NPDR | 4.04 | 0.132 | -0.080 | 0.318 | — | — | |
| 亮氨酸 | DR | 9.23 | 0.010 | -0.089 | 0.773 | — | — |
| PDR | 1.18 | 0.555 | -0.020 | 0.828 | — | — | |
| NPDR | 4.02 | 0.134 | -0.12 | 0.616 | — | — | |
| 丙氨酸 | DR | 6.38 | 0.271 | 0.039 | 0.439 | 11.22 | 0.256 |
| PDR | 3.28 | 0.658 | 0.023 | 0.516 | 4.46 | 0.696 | |
| NPDR | 1.10 | 0.954 | 0.023 | 0.676 | 1.53 | 0.958 | |
| 蛋白质 | |||||||
| 白蛋白 | DR | 0.15 | 0.930 | 0.019 | 0.878 | — | — |
| PDR | 1.48 | 0.478 | 0.092 | 0.461 | — | — | |
| NPDR | 1.16 | 0.559 | -0.082 | 0.639 | — | — | |
| 糖蛋白 | DR | 25.75 | 0.477 | -0.002 | 0.818 | 27.35 | 0.521 |
| PDR | 30.72 | 0.239 | -0.007 | 0.427 | 37.71 | 0.208 | |
| NPDR | 13.54 | 0.979 | -0.010 | 0.391 | 14.21 | 0.983 | |
| 载脂蛋白B | DR | 40.52 | 0.019 | -0.014 | 0.286 | 44.37 | 0.020 |
| PDR | 31.16 | 0.149 | 0.001 | 0.896 | 33.94 | 0.152 | |
| NPDR | 28.42 | 0.243 | -0.009 | 0.541 | 30.65 | 0.252 | |
| 载脂蛋白A1 | DR | 11.19 | 0.427 | 0.007 | 0.780 | 12.46 | 0.489 |
| PDR | 21.98 | 0.025 | 0.020 | 0.457 | 25.67 | 0.036 | |
| NPDR | 7.98 | 0.715 | 0.009 | 0.744 | 9.21 | 0.759 | |
| 糖蛋白乙酰化物 | DR | 18.41 | 0.018 | -0.070 | 0.119 | 22.60 | 0.030 |
| PDR | 28.87 | <0.001 | -0.014 | 0.780 | 35.32 | 0.001 | |
| NPDR | 15.38 | 0.052 | -0.052 | 0.355 | 19.07 | 0.068 | |
| 碳水化合物 | |||||||
| 丙酮酸 | DR | — | — | — | — | — | — |
| PDR | — | — | — | — | — | — | |
| NPDR | — | — | — | — | — | — | |
| 乳酸 | DR | 3.95 | 0.047 | — | — | — | — |
| PDR | 0.02 | 0.894 | — | — | — | — | |
| NPDR | 1.76 | 0.185 | — | — | — | — | |
| 葡萄糖 | DR | 2.59 | 0.459 | 0.016 | 0.765 | 5.06 | 0.507 |
| PDR | 0.50 | 0.918 | -0.019 | 0.651 | 1.40 | 0.868 | |
| NPDR | 0.74 | 0.864 | 0.039 | 0.559 | 0.88 | 0.916 | |
| 能量 | |||||||
| 柠檬酸 | DR | 6.25 | 0.181 | 0.018 | 0.845 | 10.83 | 0.229 |
| PDR | 2.82 | 0.588 | -0.005 | 0.932 | 4.99 | 0.574 | |
| NPDR | 6.32 | 0.176 | -0.011 | 0.927 | 9.61 | 0.243 | |
| 酮酸 | |||||||
| 乙酰乙酸 | DR | 3.32 | 0.068 | — | — | — | — |
| PDR | 1.62 | 0.203 | — | — | — | — | |
| NPDR | 1.96 | 0.162 | — | — | — | — | |
| 代谢物比例 | |||||||
| 每个双键的平均亚甲基数目 | DR | 14.65 | 0.101 | 0.006 | 0.792 | 18.03 | 0.196 |
| PDR | 4.93 | 0.841 | -0.008 | 0.596 | 5.63 | 0.878 | |
| NPDR | 8.70 | 0.465 | -0.002 | 0.915 | 9.91 | 0.572 | |
| 双烯基与双键的比率 | DR | 11.37 | 0.497 | -0.003 | 0.841 | 13.66 | 0.539 |
| PDR | 7.37 | 0.832 | 0.010 | 0.394 | 9.11 | 0.827 | |
| NPDR | 7.25 | 0.841 | -0.008 | 0.683 | 9.09 | 0.834 | |
Table 6 Heterogeneity and pleiotropy test for MR analysis results of impact of nonlipid metabolites on diabetic retinopathy
| 暴露因素 | 结局 | Cochran's Q检验 | MR Egger截距法 | MR PRESSO法 | |||
|---|---|---|---|---|---|---|---|
| Q值 | P值 | 截距 | P值 | RSSobs | P值 | ||
| 氨基酸 | |||||||
| 异亮氨酸 | DR | — | — | — | — | — | — |
| PDR | — | — | — | — | — | — | |
| NPDR | — | — | — | — | — | — | |
| 缬氨酸 | DR | 2.60 | 0.458 | -0.092 | 0.255 | 4.88 | 0.508 |
| PDR | 0.62 | 0.891 | -0.021 | 0.718 | 0.87 | 0.921 | |
| NPDR | 3.62 | 0.306 | -0.123 | 0.250 | 5.68 | 0.416 | |
| 组氨酸 | DR | 6.59 | 0.159 | 0.050 | 0.487 | 10.01 | 0.210 |
| PDR | 2.69 | 0.611 | -0.011 | 0.793 | 4.26 | 0.620 | |
| NPDR | 2.76 | 0.599 | 0.002 | 0.978 | 4.53 | 0.600 | |
| 肌氨酸 | DR | 1.82 | 0.769 | -0.019 | 0.741 | 3.12 | 0.757 |
| PDR | 2.71 | 0.608 | -0.005 | 0.915 | 4.40 | 0.616 | |
| NPDR | 2.43 | 0.657 | -0.062 | 0.426 | 3.64 | 0.686 | |
| 酪氨酸 | DR | 5.39 | 0.146 | 0.052 | 0.254 | 9.91 | 0.238 |
| PDR | 4.62 | 0.202 | 0.040 | 0.264 | 7.72 | 0.296 | |
| NPDR | 1.84 | 0.607 | 0.028 | 0.546 | 3.05 | 0.656 | |
| 谷氨酰胺 | DR | 8.83 | 0.066 | 0.050 | 0.092 | 27.08 | 0.295 |
| PDR | 2.96 | 0.564 | 0.010 | 0.594 | 4.56 | 0.646 | |
| NPDR | 2.59 | 0.629 | 0.021 | 0.482 | 4.45 | 0.670 | |
| 苯丙氨酸 | DR | 4.60 | 0.100 | -0.045 | 0.569 | — | — |
| PDR | 4.98 | 0.083 | -0.057 | 0.293 | — | — | |
| NPDR | 4.04 | 0.132 | -0.080 | 0.318 | — | — | |
| 亮氨酸 | DR | 9.23 | 0.010 | -0.089 | 0.773 | — | — |
| PDR | 1.18 | 0.555 | -0.020 | 0.828 | — | — | |
| NPDR | 4.02 | 0.134 | -0.12 | 0.616 | — | — | |
| 丙氨酸 | DR | 6.38 | 0.271 | 0.039 | 0.439 | 11.22 | 0.256 |
| PDR | 3.28 | 0.658 | 0.023 | 0.516 | 4.46 | 0.696 | |
| NPDR | 1.10 | 0.954 | 0.023 | 0.676 | 1.53 | 0.958 | |
| 蛋白质 | |||||||
| 白蛋白 | DR | 0.15 | 0.930 | 0.019 | 0.878 | — | — |
| PDR | 1.48 | 0.478 | 0.092 | 0.461 | — | — | |
| NPDR | 1.16 | 0.559 | -0.082 | 0.639 | — | — | |
| 糖蛋白 | DR | 25.75 | 0.477 | -0.002 | 0.818 | 27.35 | 0.521 |
| PDR | 30.72 | 0.239 | -0.007 | 0.427 | 37.71 | 0.208 | |
| NPDR | 13.54 | 0.979 | -0.010 | 0.391 | 14.21 | 0.983 | |
| 载脂蛋白B | DR | 40.52 | 0.019 | -0.014 | 0.286 | 44.37 | 0.020 |
| PDR | 31.16 | 0.149 | 0.001 | 0.896 | 33.94 | 0.152 | |
| NPDR | 28.42 | 0.243 | -0.009 | 0.541 | 30.65 | 0.252 | |
| 载脂蛋白A1 | DR | 11.19 | 0.427 | 0.007 | 0.780 | 12.46 | 0.489 |
| PDR | 21.98 | 0.025 | 0.020 | 0.457 | 25.67 | 0.036 | |
| NPDR | 7.98 | 0.715 | 0.009 | 0.744 | 9.21 | 0.759 | |
| 糖蛋白乙酰化物 | DR | 18.41 | 0.018 | -0.070 | 0.119 | 22.60 | 0.030 |
| PDR | 28.87 | <0.001 | -0.014 | 0.780 | 35.32 | 0.001 | |
| NPDR | 15.38 | 0.052 | -0.052 | 0.355 | 19.07 | 0.068 | |
| 碳水化合物 | |||||||
| 丙酮酸 | DR | — | — | — | — | — | — |
| PDR | — | — | — | — | — | — | |
| NPDR | — | — | — | — | — | — | |
| 乳酸 | DR | 3.95 | 0.047 | — | — | — | — |
| PDR | 0.02 | 0.894 | — | — | — | — | |
| NPDR | 1.76 | 0.185 | — | — | — | — | |
| 葡萄糖 | DR | 2.59 | 0.459 | 0.016 | 0.765 | 5.06 | 0.507 |
| PDR | 0.50 | 0.918 | -0.019 | 0.651 | 1.40 | 0.868 | |
| NPDR | 0.74 | 0.864 | 0.039 | 0.559 | 0.88 | 0.916 | |
| 能量 | |||||||
| 柠檬酸 | DR | 6.25 | 0.181 | 0.018 | 0.845 | 10.83 | 0.229 |
| PDR | 2.82 | 0.588 | -0.005 | 0.932 | 4.99 | 0.574 | |
| NPDR | 6.32 | 0.176 | -0.011 | 0.927 | 9.61 | 0.243 | |
| 酮酸 | |||||||
| 乙酰乙酸 | DR | 3.32 | 0.068 | — | — | — | — |
| PDR | 1.62 | 0.203 | — | — | — | — | |
| NPDR | 1.96 | 0.162 | — | — | — | — | |
| 代谢物比例 | |||||||
| 每个双键的平均亚甲基数目 | DR | 14.65 | 0.101 | 0.006 | 0.792 | 18.03 | 0.196 |
| PDR | 4.93 | 0.841 | -0.008 | 0.596 | 5.63 | 0.878 | |
| NPDR | 8.70 | 0.465 | -0.002 | 0.915 | 9.91 | 0.572 | |
| 双烯基与双键的比率 | DR | 11.37 | 0.497 | -0.003 | 0.841 | 13.66 | 0.539 |
| PDR | 7.37 | 0.832 | 0.010 | 0.394 | 9.11 | 0.827 | |
| NPDR | 7.25 | 0.841 | -0.008 | 0.683 | 9.09 | 0.834 | |
| 暴露 | 结局 | MR分析 | OR(95%CI) | P值 |
|---|---|---|---|---|
| 载脂蛋白B | DR | 原始值 | 0.98(0.88~1.08) | 0.660 |
| 校正值 | NA | NA | ||
| 载脂蛋白A1 | PDR | 原始值 | 0.99(0.87~1.23) | 0.890 |
| 校正值 | 0.96(0.87~1.05) | 0.370 | ||
| 糖蛋白乙酰化物 | DR | 原始值 | 0.93(0.74~1.16) | 0.540 |
| 校正值 | NA | NA | ||
| PDR | 原始值 | 1.01(0.80~1.28) | 0.940 | |
| 校正值 | 1.02(0.87~1.21) | 0.800 |
Table 7 Corrected MR analysis results of impact of nonlipid metabolites on diabetic retinopathy by MR PRESSO
| 暴露 | 结局 | MR分析 | OR(95%CI) | P值 |
|---|---|---|---|---|
| 载脂蛋白B | DR | 原始值 | 0.98(0.88~1.08) | 0.660 |
| 校正值 | NA | NA | ||
| 载脂蛋白A1 | PDR | 原始值 | 0.99(0.87~1.23) | 0.890 |
| 校正值 | 0.96(0.87~1.05) | 0.370 | ||
| 糖蛋白乙酰化物 | DR | 原始值 | 0.93(0.74~1.16) | 0.540 |
| 校正值 | NA | NA | ||
| PDR | 原始值 | 1.01(0.80~1.28) | 0.940 | |
| 校正值 | 1.02(0.87~1.21) | 0.800 |
| 暴露因素 | 结局 | 分析方法 | OR(95%CI) | SE | P值 |
|---|---|---|---|---|---|
| BMI | 异亮氨酸 | IVW | 1.21(1.14~1.30) | 0.03 | 1.0E-08 |
| weighted Median | 1.27(1.14~1.42) | 0.06 | 1.5E-05 | ||
| MR Egger回归法 | 1.35(1.14~1.58) | 0.08 | 3.9E-04 | ||
| weighted mode | 1.33(1.12~1.58) | 0.09 | 1.4E-03 | ||
| MR-RAPS | 1.22(1.16~1.28) | 0.03 | 3.4E-11 | ||
| 白蛋白 | IVW | 0.93(0.86~0.99) | 0.04 | 0.041 | |
| weighted Median | 0.93(0.80~1.06) | 0.07 | 0.278 | ||
| MR Egger回归法 | 0.91(0.76~1.09) | 0.09 | 0.300 | ||
| weighted mode | 0.89(0.73~1.08) | 0.10 | 0.243 | ||
| MR-RAPS | 0.93(0.88~0.96) | 0.03 | 0.016 | ||
| 糖蛋白 | IVW | 1.33(1.23~1.43) | 0.04 | 3.2E-14 | |
| weighted Median | 1.43(1.27~1.61) | 0.06 | 5.8E-09 | ||
| MR Egger回归法 | 1.44(1.20~1.72) | 0.09 | 9.5E-05 | ||
| weighted mode | 0.99(0.76~1.28) | 0.09 | 0.912 | ||
| MR-RAPS | 1.32(1.24~1.40) | 0.04 | 3.9E-12 | ||
| 丙酮酸 | IVW | 1.08(1.01~1.16) | 0.04 | 0.031 | |
| weighted Median | 1.11(0.97~1.25) | 0.07 | 0.117 | ||
| MR Egger回归法 | 1.17(0.99~1.39) | 0.08 | 0.064 | ||
| weighted mode | 1.08(0.92~1.27) | 0.08 | 0.350 | ||
| MR-RAPS | 1.08(1.01~1.15) | 0.03 | 0.010 | ||
| 双烯基与双键的比率 | IVW | 0.82(0.75~0.90) | 0.05 | 2.8E-05 | |
| weighted Median | 0.81(0.69~0.93) | 0.07 | 4.3E-03 | ||
| MR Egger回归法 | 0.82(0.65~1.02) | 0.11 | 0.081 | ||
| weighted mode | 0.78(0.62~0.98) | 0.11 | 0.028 | ||
| MR-RAPS | 0.82(0.77~0.88) | 0.03 | 3.7E-11 | ||
| WHR | 异亮氨酸 | IVW | 1.34(1.21~1.48) | 0.05 | 3.4E-08 |
| weighted Median | 1.46(1.27~1.67) | 0.07 | 1.4E-07 | ||
| MR Egger回归法 | 1.42(1.07~1.88) | 0.15 | 0.022 | ||
| weighted mode | 1.66(1.30~2.12) | 0.13 | 7.3E-05 | ||
| MR-RAPS | 1.36(1.24~1.47) | 0.05 | 7.7E-10 | ||
| 白蛋白 | IVW | 1.04(0.95~1.15) | 0.05 | 0.398 | |
| weighted Median | 1.00(0.86~1.16) | 0.04 | 0.970 | ||
| MR Egger回归法 | 1.08(0.83~1.40) | 0.13 | 0.547 | ||
| weighted mode | 0.90(0.61~1.31) | 0.19 | 0.582 | ||
| MR-RAPS | 1.04(0.96~1.15) | 0.04 | 0.327 | ||
| 糖蛋白 | IVW | 1.26(1.12~1.42) | 0.06 | 1.2E-04 | |
| weighted Median | 1.32(1.10~1.57) | 0.09 | 2.8E-03 | ||
| MR Egger回归法 | 1.11(0.81~1.53) | 0.16 | 0.502 | ||
| weighted mode | 0.80(0.61~1.06) | 0.15 | 0.123 | ||
| MR-RAPS | 1.26(1.14~1.40) | 0.05 | 3.8E-06 | ||
| 丙酮酸 | IVW | 1.03(0.94~1.13) | 0.05 | 0.517 | |
| weighted Median | 1.09(0.95~1.25) | 0.07 | 0.203 | ||
| MR Egger回归法 | 0.98(0.76~1.28) | 0.17 | 0.906 | ||
| weighted mode | 1.09(0.86~1.37) | 0.12 | 0.473 | ||
| MR-RAPS | 1.03(0.95~1.11) | 0.04 | 0.460 | ||
| 双烯基与双键的比率 | IVW | 0.91(0.81~1.03) | 0.06 | 0.130 | |
| weighted Median | 0.96(0.80~1.16) | 0.11 | 0.710 | ||
| MR Egger回归法 | 1.11(0.80~1.53) | 0.17 | 0.541 | ||
| weighted mode | 0.94(0.71~1.24) | 0.14 | 0.656 | ||
| MR-RAPS | 0.92(0.84~1.01) | 0.05 | 0.095 |
Table 8 MR analysis results of impact of BMI and WHR on nonlipid metabolites
| 暴露因素 | 结局 | 分析方法 | OR(95%CI) | SE | P值 |
|---|---|---|---|---|---|
| BMI | 异亮氨酸 | IVW | 1.21(1.14~1.30) | 0.03 | 1.0E-08 |
| weighted Median | 1.27(1.14~1.42) | 0.06 | 1.5E-05 | ||
| MR Egger回归法 | 1.35(1.14~1.58) | 0.08 | 3.9E-04 | ||
| weighted mode | 1.33(1.12~1.58) | 0.09 | 1.4E-03 | ||
| MR-RAPS | 1.22(1.16~1.28) | 0.03 | 3.4E-11 | ||
| 白蛋白 | IVW | 0.93(0.86~0.99) | 0.04 | 0.041 | |
| weighted Median | 0.93(0.80~1.06) | 0.07 | 0.278 | ||
| MR Egger回归法 | 0.91(0.76~1.09) | 0.09 | 0.300 | ||
| weighted mode | 0.89(0.73~1.08) | 0.10 | 0.243 | ||
| MR-RAPS | 0.93(0.88~0.96) | 0.03 | 0.016 | ||
| 糖蛋白 | IVW | 1.33(1.23~1.43) | 0.04 | 3.2E-14 | |
| weighted Median | 1.43(1.27~1.61) | 0.06 | 5.8E-09 | ||
| MR Egger回归法 | 1.44(1.20~1.72) | 0.09 | 9.5E-05 | ||
| weighted mode | 0.99(0.76~1.28) | 0.09 | 0.912 | ||
| MR-RAPS | 1.32(1.24~1.40) | 0.04 | 3.9E-12 | ||
| 丙酮酸 | IVW | 1.08(1.01~1.16) | 0.04 | 0.031 | |
| weighted Median | 1.11(0.97~1.25) | 0.07 | 0.117 | ||
| MR Egger回归法 | 1.17(0.99~1.39) | 0.08 | 0.064 | ||
| weighted mode | 1.08(0.92~1.27) | 0.08 | 0.350 | ||
| MR-RAPS | 1.08(1.01~1.15) | 0.03 | 0.010 | ||
| 双烯基与双键的比率 | IVW | 0.82(0.75~0.90) | 0.05 | 2.8E-05 | |
| weighted Median | 0.81(0.69~0.93) | 0.07 | 4.3E-03 | ||
| MR Egger回归法 | 0.82(0.65~1.02) | 0.11 | 0.081 | ||
| weighted mode | 0.78(0.62~0.98) | 0.11 | 0.028 | ||
| MR-RAPS | 0.82(0.77~0.88) | 0.03 | 3.7E-11 | ||
| WHR | 异亮氨酸 | IVW | 1.34(1.21~1.48) | 0.05 | 3.4E-08 |
| weighted Median | 1.46(1.27~1.67) | 0.07 | 1.4E-07 | ||
| MR Egger回归法 | 1.42(1.07~1.88) | 0.15 | 0.022 | ||
| weighted mode | 1.66(1.30~2.12) | 0.13 | 7.3E-05 | ||
| MR-RAPS | 1.36(1.24~1.47) | 0.05 | 7.7E-10 | ||
| 白蛋白 | IVW | 1.04(0.95~1.15) | 0.05 | 0.398 | |
| weighted Median | 1.00(0.86~1.16) | 0.04 | 0.970 | ||
| MR Egger回归法 | 1.08(0.83~1.40) | 0.13 | 0.547 | ||
| weighted mode | 0.90(0.61~1.31) | 0.19 | 0.582 | ||
| MR-RAPS | 1.04(0.96~1.15) | 0.04 | 0.327 | ||
| 糖蛋白 | IVW | 1.26(1.12~1.42) | 0.06 | 1.2E-04 | |
| weighted Median | 1.32(1.10~1.57) | 0.09 | 2.8E-03 | ||
| MR Egger回归法 | 1.11(0.81~1.53) | 0.16 | 0.502 | ||
| weighted mode | 0.80(0.61~1.06) | 0.15 | 0.123 | ||
| MR-RAPS | 1.26(1.14~1.40) | 0.05 | 3.8E-06 | ||
| 丙酮酸 | IVW | 1.03(0.94~1.13) | 0.05 | 0.517 | |
| weighted Median | 1.09(0.95~1.25) | 0.07 | 0.203 | ||
| MR Egger回归法 | 0.98(0.76~1.28) | 0.17 | 0.906 | ||
| weighted mode | 1.09(0.86~1.37) | 0.12 | 0.473 | ||
| MR-RAPS | 1.03(0.95~1.11) | 0.04 | 0.460 | ||
| 双烯基与双键的比率 | IVW | 0.91(0.81~1.03) | 0.06 | 0.130 | |
| weighted Median | 0.96(0.80~1.16) | 0.11 | 0.710 | ||
| MR Egger回归法 | 1.11(0.80~1.53) | 0.17 | 0.541 | ||
| weighted mode | 0.94(0.71~1.24) | 0.14 | 0.656 | ||
| MR-RAPS | 0.92(0.84~1.01) | 0.05 | 0.095 |
| 暴露因素 | 结局 | Cochran's Q检验 | MR Egger回归法 | ||
|---|---|---|---|---|---|
| Q值 | P值 | 截距 | P值 | ||
| BMI | 异亮氨酸 | 312.75 | 0.460 | -0.002 | 0.170 |
| 白蛋白 | 286.38 | 0.840 | 0.000 4 | 0.790 | |
| 糖蛋白 | 307.72 | 0.540 | -0.002 | 0.340 | |
| 丙酮酸 | 329.34 | 0.230 | -0.001 6 | 0.280 | |
| 双烯基与双键的比率 | 334.75 | 0.170 | 0.0001 | 0.950 | |
| WHR | 异亮氨酸 | 316.56 | <0.001 | -0.001 | 0.650 |
| 白蛋白 | 223.83 | 0.210 | -0.000 7 | 0.760 | |
| 糖蛋白 | 340.36 | <0.001 | 0.002 | 0.420 | |
| 丙酮酸 | 265.59 | <0.001 | 0.0009 | 0.710 | |
| 双烯基与双键的比率 | 247.40 | 0.030 | -0.004 | 0.200 | |
Table 9 Heterogeneity and pleiotropy test for MR analysis results of impact of BMI and WHR on nonlipid metabolites
| 暴露因素 | 结局 | Cochran's Q检验 | MR Egger回归法 | ||
|---|---|---|---|---|---|
| Q值 | P值 | 截距 | P值 | ||
| BMI | 异亮氨酸 | 312.75 | 0.460 | -0.002 | 0.170 |
| 白蛋白 | 286.38 | 0.840 | 0.000 4 | 0.790 | |
| 糖蛋白 | 307.72 | 0.540 | -0.002 | 0.340 | |
| 丙酮酸 | 329.34 | 0.230 | -0.001 6 | 0.280 | |
| 双烯基与双键的比率 | 334.75 | 0.170 | 0.0001 | 0.950 | |
| WHR | 异亮氨酸 | 316.56 | <0.001 | -0.001 | 0.650 |
| 白蛋白 | 223.83 | 0.210 | -0.000 7 | 0.760 | |
| 糖蛋白 | 340.36 | <0.001 | 0.002 | 0.420 | |
| 丙酮酸 | 265.59 | <0.001 | 0.0009 | 0.710 | |
| 双烯基与双键的比率 | 247.40 | 0.030 | -0.004 | 0.200 | |
| 暴露因素 | 结局 | 中介因素 | 直接作用 | 中介作用 | ||||
|---|---|---|---|---|---|---|---|---|
| β | 95%CI | P值 | β | 95%CI | P值 | |||
| BMI | DR | 异亮氨酸 | 0.81 | — | — | -0.16 | -0.26~-0.05 | 0.019 |
| 糖蛋白 | 0.72 | — | — | -0.05 | -0.06~-0.02 | 0.029 | ||
| 白蛋白 | 1.07 | — | — | 0.05 | -0.05~0.16 | 0.620 | ||
| 丙酮酸 | 0.92 | — | — | -0.07 | -0.11~-0.03 | 0.027 | ||
| 双烯基与双键的比率 | 1.19 | — | — | 0.02 | 0.01~0.03 | 0.036 | ||
| WHR | 异亮氨酸 | 0.71 | — | — | -0.21 | -0.27~-0.15 | 7.2E-04 | |
| 糖蛋白 | 0.77 | — | — | -0.03 | -0.05~-0.02 | 0.031 | ||
| BMI | PDR | 白蛋白 | 1.07 | — | — | 0.11 | -0.08~0.30 | 0.560 |
| BMI | NPDR | 糖蛋白 | 0.72 | — | — | -0.04 | -0.06~-0.02 | 0.032 |
| 白蛋白 | 1.07 | — | — | 0.04 | -0.07~0.15 | 0.390 | ||
| WHR | 糖蛋白 | 0.77 | — | — | -0.03 | -0.06~-0.01 | 0.190 | |
Table 10 Two step MR analysis results of mediating effect of nonlipid metabolites between obesity and diabetic retinopathy
| 暴露因素 | 结局 | 中介因素 | 直接作用 | 中介作用 | ||||
|---|---|---|---|---|---|---|---|---|
| β | 95%CI | P值 | β | 95%CI | P值 | |||
| BMI | DR | 异亮氨酸 | 0.81 | — | — | -0.16 | -0.26~-0.05 | 0.019 |
| 糖蛋白 | 0.72 | — | — | -0.05 | -0.06~-0.02 | 0.029 | ||
| 白蛋白 | 1.07 | — | — | 0.05 | -0.05~0.16 | 0.620 | ||
| 丙酮酸 | 0.92 | — | — | -0.07 | -0.11~-0.03 | 0.027 | ||
| 双烯基与双键的比率 | 1.19 | — | — | 0.02 | 0.01~0.03 | 0.036 | ||
| WHR | 异亮氨酸 | 0.71 | — | — | -0.21 | -0.27~-0.15 | 7.2E-04 | |
| 糖蛋白 | 0.77 | — | — | -0.03 | -0.05~-0.02 | 0.031 | ||
| BMI | PDR | 白蛋白 | 1.07 | — | — | 0.11 | -0.08~0.30 | 0.560 |
| BMI | NPDR | 糖蛋白 | 0.72 | — | — | -0.04 | -0.06~-0.02 | 0.032 |
| 白蛋白 | 1.07 | — | — | 0.04 | -0.07~0.15 | 0.390 | ||
| WHR | 糖蛋白 | 0.77 | — | — | -0.03 | -0.06~-0.01 | 0.190 | |
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