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Evaluating the causal association between microRNAs and amyotrophic lateral sclerosis

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Abstract

Background

Currently, miRNAs are involved in the development of amyotrophic lateral sclerosis (ALS), and identifying circulating miRNAs that are causally associated with ALS risk as biomarkers is imperative.

Methods

We performed a two-sample Mendelian randomization study to evaluate the causal relationship between miRNAs and ALS. Our analysis was conducted using summary statistics from miRNA expression quantitative loci (eQTL) data of the Framingham Heart Study and ALS genome-wide association studies data. Another independent miRNA data was used to further validate.

Results

We identified eight unique miRNAs that were causally associated with ALS risk. Using expression data of miRNAs from an independent study, we validated three high-confidence miRNAs, namely hsa-miR-27b-3p, hsa-miR-139-5p, and hsa-miR-152-3p, which might have a potential causal effect on ALS risk.

Conclusion

We suggested that higher levels of hsa-miR-27b-3p and hsa-miR-139-5p had protective effects on ALS, whereas higher levels of hsa-miR-152-3p might act as a risk factor for ALS. The analytical framework presented in this study helps to understand the role of miRNAs in the development of ALS and to identify the biomarkers for ALS risk.

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Data availability

The data used to perform the analyses in this study were obtained from public genome-wide association studies summary statistics. Validation data were obtained from the study [26] through a request to the authors.

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Acknowledgements

We thank all the GWAS consortiums for making the summary data publicly available, and we are grateful to all the investigators and participants who contributed to those studies. We thank Majid Nikpay for providing the miRNA eQTL data used in this study for validation.

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Authors and Affiliations

  1. Medical School of Chinese PLA, Beijing, China

    Yahui Zhu, Zhengqing He, Wenxiu Yu, Jinghong Zhang & Jiao Wang

  2. Department of Neurology, the First Medical Center, Chinese PLA General Hospital, Beijing, China

    Yahui Zhu, Mao Li, Zhengqing He, Xinyuan Pang, Rongrong Du, Wenxiu Yu, Jinghong Zhang, Jiongming Bai, Jiao Wang & Xusheng Huang

  3. College of Medicine, Nankai University, Tianjin, China

    Xinyuan Pang, Rongrong Du & Jiongming Bai

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  1. Yahui Zhu
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  2. Mao Li
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Contributions

Conceptualization: Xusheng Huang; methodology: Yahui Zhu, Mao Li, Zhengqing He, Xinyuan Pang, Rongrong Du; formal analysis and investigation: Yahui Zhu, Mao Li, Zhengqing He, Xinyuan Pang, Rongrong Du, Wenxiu Yu, Jinghong Zhang, Jiongming Bai, Jiao Wang; writing – original draft preparation: Yahui Zhu; writing – review and editing: Xusheng Huang; resources: Yahui Zhu; supervision: Xusheng Huang. All authors approved the version to be published.

Corresponding author

Correspondence to Xusheng Huang.

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Ethical approval

Ethical review and approval were waived for this study due to this study used summary data from GWAS and did not involve individual data. All studies that contributed data to this analysis were approved by the relevant institutional review board. 

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Patient informed consent was waived due to this study used summary data from GWAS and did not involve individual data.

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Patient consent was waived due to this study used summary data from GWAS and did not involve individual data.

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The authors declare no competing interests.

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Zhu, Y., Li, M., He, Z. et al. Evaluating the causal association between microRNAs and amyotrophic lateral sclerosis. Neurol Sci 44, 3567–3575 (2023). https://doi.org/10.1007/s10072-023-06860-3

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