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Genetically predicted telomere length and the risk of 11 hematological diseases: a Mendelian randomization study - PubMed

  • ️Mon Jan 01 2024

Genetically predicted telomere length and the risk of 11 hematological diseases: a Mendelian randomization study

Yimin Wang et al. Aging (Albany NY). 2024.

Abstract

Objective: Previous studies have demonstrated that various hematologic diseases (HDs) induce alterations in telomere length (TL). The aim of this study is to investigate whether genetically predicted changes in TL have an impact on the risk of developing HDs.

Methods: GWAS data for TL and 11 HDs were extracted from the database. The R software package "TwoSampleMR" was employed to conduct a two-sample Mendelian randomization (MR) analysis, in order to estimate the influence of TL changes on the risk of developing the 11 HDs.

Results: We examined the effect of TL changes on the risk of developing the 11 HDs. The IVW results revealed a significant causal association between genetically predicted longer TL and the risk of developing acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MANTLE), and hodgkin lymphoma (HODGKIN). However, there was no significant causal relationship observed between TL changes and the risk of developing chronic myeloid leukemia (CML), diffuse large b-cell lymphoma (DLBCL), marginal zone b-cell lymphoma (MARGINAL), follicular lymphoma (FOLLICULAR), monocytic leukemia (MONOCYTIC), and mature T/NK-cell lymphomas (TNK).

Conclusions: The MR analysis revealed a positive association between genetically predicted longer TL and an increased risk of developing ALL, AML, CLL, MANTLE, and HODGKIN. This study further supports the notion that cells with longer TL have greater proliferative and mutational potential, leading to an increased risk of certain HDs.

Keywords: GWAS data; Mendelian randomization; hematologic diseases; single nucleotide polymorphisms; telomere length.

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Conflict of interest statement

CONFLICTS OF INTEREST: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1

Schematic diagram illustrating the MR. Abbreviations: SNP: single nucleotide polymorphism; TL: telomere length; MR: Mendelian randomization; HDs: hematologic diseases.

Figure 2
Figure 2

Forest plot illustrating the association between genetically predicted TL and 11 HDs. Abbreviations: TL: telomere length; HDs: hematologic diseases; IVW-RE: inverse variance weighted (random effects); IVW-FE: inverse variance weighted (fixed effects); OR: odds ratio; CI: confidence interval; ALL: acute lymphocytic leukemia; AML: acute myeloid leukemia; CLL: chronic lymphocytic leukemia; CML: chronic myeloid leukemia; DLBCL: diffuse large b-cell lymphoma; FOLLICULAR: follicular lymphoma; HODGKIN: Hodgkin lymphoma; MANTLE: mantle cell lymphoma; MARGINAL: marginal zone b-cell lymphoma; MONOCYTIC: monocytic leukemia; TNK: mature T/NK-cell lymphomas.

Figure 3
Figure 3

Six MR methods demonstrated the causal effect of TL on HDs. (A) Scatter plot illustrating the association between TL and ALL. (B) Scatter plot illustrating the association between TL and AML. (C) Scatter plot illustrating the association between TL and CLL. (D) Scatter plot illustrating the association between TL and HODGKIN. (E) Scatter plot illustrating the association between TL and MANTLE. Abbreviations: MR: Mendelian randomization; TL: telomere length; HDs: hematologic diseases; ALL: acute lymphocytic leukemia; AML: acute myeloid leukemia; CLL: chronic lymphocytic leukemia; HODGKIN: Hodgkin lymphoma; MANTLE: mantle cell lymphoma.

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