Apply multiple genetic variants as instrumental variables—Response to “MTHFR C677T polymorphism and hypertension”

Dear Editor,

Recently, we published an article titled “Evidence on the causal link between homocysteine and hypertension from a meta‐analysis of 40 173 individuals implementing Mendelian randomization” in the journal of clinical hypertension.1 Subsequently, a letter named “MTHFR C677T polymorphism and hypertension” showed great interest to our paper. It is an honor for us to reply. As we all know, a variable must meet certain conditions for being used as an instrumental variable in Mendelian Randomization. Obviously, we clearly clarified this issue in our published paper. Therefore, the results in our paper are totally correct by applying Mendelian Randomization to demonstrate that there exists evidence on causal link between Hcy concentration and the risk of hypertension. As for the accuracy of results, we believe that using only one SNP as an instrumental variable is worth exploring, so thanks for the authors of the letter reminding us of this issue. Many other genetic factors might be associated with homocysteine and hypertension except MTHFR C677T polymorphism. If they meet the conditions for being used as instrumental variables in Mendelian Randomization, then they can be employed together because there exists publication to support it.2 We are working on it now, and there will be a series of research output.

CONFLICT OF INTEREST

None.

Funding information

This study was supported by grants to YQH from the National Natural Science Foundation of China (grants no. 11971117, 11571082) and Key Research Project of the Ministry of Science and Technology of China (grant no. 2016YFC0904400).