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

PeerJ

article

Likui Lu¹  Hongtao Zeng¹  Bangbei Wan²  Miao Sun¹ 

[1] The First Affiliated Hospital of Soochow University, Institute for Fetology;Hainan Women and Children’s Medical Center, Reproductive Medical Center;Central South University Xiangya School of Medicine Affiliated Haikou Hospital, Department of Urology;Dushu Lake Hospital Affiliated to Soochow University, Suzhou, Jiangsu Province

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

DOI  :  10.7717/peerj.15129

学科分类：社会科学、人文和艺术（综合）

来源: Inra

【 摘 要 】

ObjectiveWe aim to test whether leukocyte telomere length (LTL) is causally associated with the risk of bipolar disorder (BD) using the Mendelian randomization (MR) method.MethodsResults 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.ResultsTwo-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).ConclusionOur 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.

【 授权许可】

CC BY