Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis

Likui Lu; Hongtao Zeng; Bangbei Wan; Miao Sun

doi:10.7717/peerj.15129

Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis

PeerJ. 2023 Mar 31:11:e15129. doi: 10.7717/peerj.15129. eCollection 2023.

Authors

Likui Lu^#¹, Hongtao Zeng^#¹, Bangbei Wan^{2

3}, Miao Sun^{1

4}

Affiliations

¹ The First Affiliated Hospital of Soochow University, Institute for Fetology, Suzhou, Jiangsu, China.
² Hainan Women and Children's Medical Center, Reproductive Medical Center, Haikou, Hainan, China.
³ Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Department of Urology, Haikou, Hainan, China.
⁴ Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province, China.

^# Contributed equally.

Abstract

Objective: We aim to test whether leukocyte telomere length (LTL) is causally associated with the risk of bipolar disorder (BD) using the Mendelian randomization (MR) method.

Methods: Results of a genome-wide association study (GWAS) conducted with 472,174 individuals of European descent were used to screen for single-nucleotide polymorphisms (SNPs) related with LTL traits. Summary-level data for BD (7,647 cases and 27,303 controls) were obtained from UK Biobank. An inverse-variance-weighted (IVW) method was employed as the primary MR analysis. Sensitivity analyses were conducted via MR-Egger, maximum likelihood, MR-pleiotropy residual sum outlier (MR-PRESSO), and MR-robust adjusted profile score (MR-RAPS) methods. Finally, the MR Steiger test was utilized to validate the hypothesized relationship between exposure and outcome.

Results: Two-sample MR analysis revealed inverse relationships between genetically predicted LTL and BD risk (IVW OR [odds ratio] = 0.800, 95% CI [0.647-0.989] P = 0.039). Genetically predicted LTL exhibits a consistent connection with BD across five MR methods. Sensitivity analyses showed that the genetically determined effect of LTL on BD was stable and reliable. Furthermore, the MR Steiger test demonstrated that LTL was causal for BD rather than the opposite (P < 0.001).

Conclusion: Our findings show that genetically determined LTL reduces the risk of BD. More research is required to clarify the mechanisms underlying this apparent causal connection. In addition, these findings may be useful for developing strategies for the prevention and treatment of BD.

Keywords: Bipolar disorder; Genome-wide association study; Leukocyte telomere length; Mendelian randomization; Single-nucleotide polymorphisms; Spinal stenosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Bipolar Disorder*
Genome-Wide Association Study
Humans
Leukocytes
Mendelian Randomization Analysis
Telomere

Grants and funding

This work was supported by grants from the National Key R&D Program of China (2019YFA0802600), the National Natural Science Foundation of China (81974244), the Hainan Province Clinical Medical Center (QWYH202175), the Research and Cultivation Fund of Hainan Medical University (HYPY2020015), and the Postgraduate Research & Practice Innovation Program of Jiangsu Province (KYCX21-2972). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.