Unit of Cardiovascular and Nutritional Epidemiology, Institute of Environmental Medicine, Karolinska Institutet, Nobelsväg 13, 17177, Stockholm, Sweden.
Coagulation Unit, Department of Hematology, Karolinska University Hospital, Stockholm, Sweden.
J Thromb Thrombolysis. 2022 Jan;53(1):43-50. doi: 10.1007/s11239-021-02494-4. Epub 2021 May 27.
Whether renal function is causally associated with venous thromboembolism (VTE) is not yet fully elucidated. We conducted a two-sample Mendelian randomization (MR) study to determine the causal effect of renal function, measured as estimated glomerular filtration rate (eGFR), on VTE. Single-nucleotide polymorphisms associated with eGFR were selected as instrumental variables at the genome-wide significance level (p < 5 × 10) from a meta-analysis of 122 genome-wide association studies including up to 1,046,070 individuals. Summary-level data for VTE were obtained from the FinnGen consortium (6913 VTE cases and 169,986 non-cases) and UK Biobank study (4620 VTE cases and 356,574 non-cases). MR estimates were calculated using the random-effects inverse-variance weighted method and combined using fixed-effects meta-analysis. Genetically predicted decreased eGFR was significantly associated with an increased risk of VTE in both FinnGen and UK Biobank. For one-unit decrease in log-transformed eGFR, the odds ratios of VTE were 2.93 (95% confidence interval (CI) 1.25, 6.84) and 4.46 (95% CI 1.59, 12.5) when using data from FinnGen and UK Biobank, respectively. The combined odds ratio was 3.47 (95% CI 1.80, 6.68). Results were consistent in all sensitivity analyses and no horizontal pleiotropy was detected. This MR-study supported a casual role of impaired renal function in VTE.
肾功能与静脉血栓栓塞症（VTE）是否存在因果关系尚不完全清楚。我们进行了一项两样本孟德尔随机化（MR）研究，以确定肾功能（以估算肾小球滤过率[eGFR]衡量）与 VTE 之间的因果关系。在一项包含多达 1046070 人的 122 项全基因组关联研究的荟萃分析中，选择与 eGFR 相关的单核苷酸多态性作为全基因组显著水平（p<5×10）的工具变量。VTE 的汇总水平数据来自芬兰基因联合会（6913 例 VTE 病例和 169986 例非病例）和英国生物银行研究（4620 例 VTE 病例和 356574 例非病例）。MR 估计值是使用随机效应逆方差加权法计算的，并使用固定效应荟萃分析进行组合。在芬兰基因联合会和英国生物银行研究中，预测的 eGFR 降低与 VTE 风险增加显著相关。在对 log 转换的 eGFR 进行单位降低时，VTE 的比值比分别为 2.93（95%置信区间[CI]1.25，6.84）和 4.46（95%CI1.59，12.5）。当使用芬兰基因联合会和英国生物银行研究的数据时，合并比值比为 3.47（95%CI1.80，6.68）。所有敏感性分析的结果均一致，且未检测到水平遗传异质性。这项 MR 研究支持肾功能受损在 VTE 中起因果作用。
