Abuduxukuer Reziya, Niu Peng-Peng, Guo Zhen-Ni, Xu Yu-Ming, Yang Yi
Stroke Center, Department of Neurology, The First Hospital of Jilin University, Changchun, China.
Department of Neurology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
Neurol Ther. 2022 Dec;11(4):1677-1689. doi: 10.1007/s40120-022-00398-w. Epub 2022 Sep 1.
Preclinical studies have indicated insulin-like growth factor 1 (IGF1) as a novel therapeutic target in the treatment of migraines. We aimed to investigate the causal effect of circulating IGF1 levels on migraine risk using the two-sample Mendelian randomization method.
A total of 431 independent variants from 363,228 unrelated individuals in the UK Biobank were used as genetic instruments for circulating IGF1 levels. Summary-level data for migraines were obtained from two independent studies with 10,536 and 28,852 migraine cases, respectively.
Mendelian randomization using inverse-variance weighting showed that increased IGF1 levels were significantly associated with decreased risk of migraines in both outcome datasets (odds ratio 0.905, 95% confidence interval 0.842-0.972, p = 0.006; odds ratio 0.929, 95% confidence interval 0.882-0.979, p = 0.006). Although some other robust Mendelian randomization methods did not demonstrate a significant association, no unbalanced horizontal pleiotropy was found by Mendelian randomization-Egger regression (p values for horizontal pleiotropy 0.232 and 0.435). The effect was confirmed in additional analyses including multivariable Mendelian randomization analyses.
This two-sample Mendelian randomization study showed that genetically determined increased IGF1 levels are causally associated with decreased migraine risk. Future randomized controlled trials are warranted to confirm the benefits of IGF1 administration on migraines.
临床前研究表明，胰岛素样生长因子1（IGF1）是治疗偏头痛的一个新的治疗靶点。我们旨在使用两样本孟德尔随机化方法研究循环IGF1水平对偏头痛风险的因果效应。
英国生物银行中363228名无亲缘关系个体的431个独立变异被用作循环IGF1水平的遗传工具。偏头痛的汇总数据分别来自两项独立研究，病例数分别为10536例和28852例。
使用逆方差加权的孟德尔随机化显示，在两个结果数据集中，IGF1水平升高均与偏头痛风险降低显著相关（优势比0.905，95%置信区间0.842 - 0.972，p = 0.006；优势比0.929，95%置信区间0.882 - 0.979，p = 0.006）。尽管其他一些稳健的孟德尔随机化方法未显示出显著关联，但孟德尔随机化 - 伊格回归未发现不平衡的水平多效性（水平多效性的p值分别为0.232和0.435）。在包括多变量孟德尔随机化分析在内的额外分析中证实了该效应。
这项两样本孟德尔随机化研究表明，基因决定的IGF1水平升高与偏头痛风险降低存在因果关联。未来有必要进行随机对照试验，以证实给予IGF1对偏头痛的益处。
