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DOI 10.18632/aging.205583

Медицинская библиотека · Aging · 2024

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

Datar Sanjeev A, Werry Nicholas, Brown Austin R, Fitzpatrick Devon S, Falade Oluwafemi, Trott Josephine F, Hutchings Rachel, Amin Elena K, Morgan Jessica M, Nawaytou Hythem, Deutsch Gail H, Johnson Eric G, Gonzales Viera Omar A, Bishop Thomas F, Beach Tara Urbano, McNabb Bret R, Austin Eric D, Fineman Jeffery R, Van Eenennaam Alison L

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Аннотация

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.

Для цитирования: Datar Sanjeev A, Werry Nicholas, Brown Austin R, Fitzpatrick Devon S, Falade Oluwafemi, Trott Josephine F, Hutchings Rachel, Amin Elena K, Morgan Jessica M, Nawaytou Hythem, Deutsch Gail H, Johnson Eric G, Gonzales Viera Omar A, Bishop Thomas F, Beach Tara Urbano, McNabb Bret R, Austin Eric D, Fineman Jeffery R, Van Eenennaam Alison L. Genetically predicted telomere length and the risk of 11 hematological diseases: a Mendelian randomization study.. Aging. 2024. DOI: 10.18632/aging.205583.

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