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. 2024 Sep 16;14(1):21594.
doi: 10.1038/s41598-024-72281-7.

Proteomic Mendelian randomization to identify protein biomarkers of telomere length

Jiaxuan Zhao  1   2 , Kun Yang  1   2 , Yunfei Lu  1   2 , Linfeng Zhou  1   2 , Haoran Fu  1   2 , Jingbo Feng  3 , Jinghua Wu  4   5
Affiliations

Proteomic Mendelian randomization to identify protein biomarkers of telomere length

Jiaxuan Zhao et al. Sci Rep. .

Abstract

Shortening of telomere length (TL) is correlated with many age-related disorders and is a hallmark of biological aging. This study used proteome-wide Mendelian randomization to identify the protein biomarkers associated with telomere length. Protein quantitative trait loci (pQTL) were derived from two studies, the deCODE Health study (4907 plasma proteins) and the UK Biobank Pharma Proteomics Project (2923 plasma proteins). Summary data from genome-wide association studies (GWAS) for TL were obtained from the UK Biobank (472,174 cases) and GWAS Catalog (418,401 cases). The association between proteins and TL was further assessed using colocalization and summary data-based Mendelian randomization (SMR) analyses. The protein-protein network, druggability assessment, and phenome-wide MR were used to further evaluate the potential biological effects, druggability, and safety of the target proteins. Proteome-wide MR analysis identified 22 plasma proteins that were causally associated with telomere length. Five of these proteins (APOE, SPRED2, MAX, RALY, and PSMB1) had the highest evidence of association with TL and should be prioritized. This study revealed telomere length-related protein biomarkers, providing new insights into the development of new treatment targets for chronic diseases and anti-aging intervention strategies.

Keywords: Mendelian randomization; Protein; Telomere length.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
Overall framework of the study design.
Fig. 2
Fig. 2
Summary data from the two-stage MR (discovery and replication) and colocalization analysis on the causal relationship between proteins and TL. (A) Volcano plot of the MR results in the discovery stage between 22 plasma proteins and TL. The tagged proteins passed multiple test corrections (p < 1.91 × 10–5). (B) Bubble plot showing the results of colocalization analysis between plasma proteins and TL. (C) MR analysis of 22 proteins in the discovery and replication datasets.
Fig. 3
Fig. 3
PPI network and GO enrichment analysis of 22 proteins from discovery stage MR. (A) PPI network of proteins associated with TL. (B) GO enrichment of proteins associated with TL. BP biological processes, MF molecular functions, CC cellular components.
Fig. 4
Fig. 4
Manhattan plot for MR-PheWAS results of five proteins in Tier 1. Each dot symbolizes a disease trait, and different colors represent MR results for different protein expressions.
See this image and copyright information in PMC

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