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Causal relationship between telomere length and osteonecrosis: Bidirectional two-sample Mendelian randomization

Hao Liu1, Wei Yan2, Jinsong Li2

  • 1The First Clinical College of Medicine, Shandong University of Traditional Chinese Medicine, Jinan, Shandong Province, China.

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Shorter telomere length (TL) genetically increases the risk of developing osteonecrosis. However, osteonecrosis does not appear to affect telomere length, according to this genetic study.

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Area of Science:

  • Genetics
  • Bone Biology
  • Epidemiology

Background:

  • Telomere length (TL) shortening is linked to poor bone health.
  • A direct genetic link between TL and osteonecrosis is not well-established.

Purpose of the Study:

  • To investigate the potential causal relationship between telomere length and osteonecrosis.
  • To determine if shorter TL increases osteonecrosis risk or vice versa using Mendelian randomization.

Main Methods:

  • Bidirectional two-sample Mendelian randomization (MR) analysis.
  • Utilized genome-wide association study data for TL and osteonecrosis from large biobanks.
  • Employed various MR methods, including inverse variance weighting and MR-Egger, with heterogeneity and pleiotropy assessments.

Main Results:

  • Forward MR analysis showed genetically predicted shorter TL significantly increases osteonecrosis risk (OR=0.611, P=0.028).
  • Reverse MR analysis found no significant causal effect of osteonecrosis on TL (OR=0.999, P=0.802).
  • Robustness checks confirmed findings and indicated no significant horizontal pleiotropy or heterogeneity.

Conclusions:

  • Shorter telomere length is a significant genetic risk factor for developing osteonecrosis.
  • Osteonecrosis does not appear to causally influence telomere length.