Gut microbiome and frailty: insight from genetic correlation and mendelian randomization

ABSTRACT

Observational studies have shown that the gut microbiome is associated with frailty. However, whether these associations underlie causal effects remains unknown. Thus, this study aimed to assess the genetic correlation and causal relationships between the genetically predicted gut microbiome and frailty using linkage disequilibrium score regression (LDSC) and Mendelian Randomization (MR). Summary statistics for the gut microbiome were obtained from a genome-wide association study (GWAS) meta-analysis of the MiBioGen consortium (N = 18,340). Summary statistics for frailty were obtained from a GWAS meta-analysis, including the UK Biobank and TwinGene (N = 175,226). We used LDSC and MR analyses to estimate the genetic correlation and causality between the genetically predicted gut microbiome and frailty. Our findings indicate a suggestive genetic correlation between Christensenellaceae R-7 and frailty. Moreover, we found evidence for suggestive causal effects of twelve genus-level gut microbes on frailty using at least two MR methods. There was no evidence of horizontal pleiotropy or heterogeneity in the MR analysis. This study provides suggestive evidence for a potential genetic correlation and causal association between several genetically predicted gut microbes and frailty. More population-based observational studies and animal experiments are required to clarify this association and the underlying mechanisms.

KEYWORDS:

• Gut microbes
• frailty
• genetic correlation
• mendelian randomization

Acknowledgments

The authors thank the participants and investigators of all GWAS included in this work. The authors also thank the MiBioGen Consortium, UK Biobank, and Swedish TwinGene for making the summary data openly available. Thanks to Figdraw for providing the materials in Figure 1.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contributions

Guanghui Cui, Shaojie Li, and Xuezhi Zhang contributed to study design. Guanghui Cui and Shaojie Li analyzed the data and drafted the manuscript. Yao Yang, Xiaofen Jia, Miaomiao Lin, Yue Feng, Zicheng Wang, Yingming Chu and Zongming Shi compiled the data and provided comments on the draft. Hui Ye and Xuezhi Zhang revised the manuscript. All authors have read and approved the final manuscript.

Data availability statement

The datasets analyzed in the current study can be downloaded from the website https://mibiogen.gcc.rug.nl/, https://www.ebi.ac.uk/gwas/downloads/summary-statistics.

Ethics approval

The datasets used in the current study were publicly available and ethical approval and informed consent were obtained prior to implementation. Therefore, our study did not require any additional informed consent or ethical approval.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/19490976.2023.2282795.

Additional information

Funding

This study was supported by the National Natural Science Foundation of China (Nos.81803910 and 81973615), Capital’s Funds for Health, and the Qi-Huang Scholar Chief Scientist Program of National Administration of Traditional Chinese Medicine Leading Talents Support Program (2021).