血清生长分化因子15水平与慢性淋巴细胞白血病发生风险的关联研究

目的 采用两样本孟德尔随机化研究方法探讨血清生长分化因子15(GDF15)水平与慢性淋巴细胞白血病(CLL)发生之间的关联。方法 基于欧洲人群血清GDF15和CLL的全基因组关联研究公开数据库,筛选与血清GDF15水平相关的遗传变异位点作为工具变量,采用逆方差加权法评估遗传学预测的血清GDF15浓度与CLL发生的关联,采用最大似然比法进行敏感性分析,采用MR-Egger回归探讨工具变量潜在多效性。结果 研究共纳入3个单核苷酸多态位点作为工具变量,逆方差加权法结果显示,血清GDF15水平与CLL发生风险之间存在负相关,GDF15浓度每升高一个标准差(SD),CLL发生风险降低33%(95%置信区间:2%～54%)(P=0.039)。敏感性分析得到了一致的结果。此外,MR-Egger回归未发现存在多效性。结论 本研究结果提示,在欧洲人群中,血清GDF15水平与CLL发生之间可能存在负相关,仍需大样本人群研究及体内外实验进一步阐明GDF15在CLL发生发展中的作用及其潜在生物学机制。

Genetically predicted growth differentiation factor15 levels and risk of chronic lymphocytic leukemia

Objective To investigate the potential causal associations of serum growth differentiation factor 15(GDF15)levels with the risk of chronic lymphocytic leukemia(CLL)using a Mendelian randomization(MR)design. Methods Based on public genome-wide association study databases of serum GDF15 and CLL from European populations, genetic variants associated with serum GDF15 levels were selected and used as instrumental variables. Inverse-variance weighted method was used to assess the association of genetically predicted serum GDF15 concentrations with CLL risk. Sensitivity analyses were performed using the maximum likelihood-based method. MR-Egger regression was used to detect potential pleiotropy. Results A total of three single nucleotide polymorphisms(SNPs)were used as instrumental variables. Genetically predicted high serum GDF15 levels were associated with a decreased risk of CLL. Each standard deviation(SD)increase in GDF15 concentration was associated with a 33% reduction in the risk of CLL(95%CI: 2%-54%)(P=0.039), with similar result in the sensitivity analysis. Moreover, no evidence of pleiotropy was detected by MR-Egger regression. Conclusion Our study suggested an inverse association between serum GDF15 levels and risk of CLL among European populations. Large population studies and experiments in vitro and in vivo are warranted to elucidate the biological mechanism of GDF15 on the development of CLL.