Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis
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...
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PeerJ Inc.
2023-03-01
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| Online Access: | https://peerj.com/articles/15129.pdf |
| _version_ | 1797418171312898048 |
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| author | Likui Lu Hongtao Zeng Bangbei Wan Miao Sun |
| author_facet | Likui Lu Hongtao Zeng Bangbei Wan Miao Sun |
| author_sort | Likui Lu |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T06:29:44Z |
| format | Article |
| id | doaj.art-30357b54ea814391ba26e9be8ae847f0 |
| institution | Directory Open Access Journal |
| issn | 2167-8359 |
| language | English |
| last_indexed | 2024-03-09T06:29:44Z |
| publishDate | 2023-03-01 |
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| spelling | doaj.art-30357b54ea814391ba26e9be8ae847f02023-12-03T11:09:38ZengPeerJ Inc.PeerJ2167-83592023-03-0111e1512910.7717/peerj.15129Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysisLikui Lu0Hongtao Zeng1Bangbei Wan2Miao Sun3The First Affiliated Hospital of Soochow University, Institute for Fetology, Suzhou, Jiangsu, ChinaThe First Affiliated Hospital of Soochow University, Institute for Fetology, Suzhou, Jiangsu, ChinaHainan Women and Children’s Medical Center, Reproductive Medical Center, Haikou, Hainan, ChinaThe First Affiliated Hospital of Soochow University, Institute for Fetology, Suzhou, Jiangsu, ChinaObjective 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.https://peerj.com/articles/15129.pdfLeukocyte telomere lengthBipolar disorderMendelian randomizationGenome-wide association studySingle-nucleotide polymorphismsSpinal stenosis |
| spellingShingle | Likui Lu Hongtao Zeng Bangbei Wan Miao Sun Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis PeerJ Leukocyte telomere length Bipolar disorder Mendelian randomization Genome-wide association study Single-nucleotide polymorphisms Spinal stenosis |
| title | Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis |
| title_full | Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis |
| title_fullStr | Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis |
| title_full_unstemmed | Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis |
| title_short | Leukocyte telomere length and bipolar disorder risk: evidence from Mendelian randomization analysis |
| title_sort | leukocyte telomere length and bipolar disorder risk evidence from mendelian randomization analysis |
| topic | Leukocyte telomere length Bipolar disorder Mendelian randomization Genome-wide association study Single-nucleotide polymorphisms Spinal stenosis |
| url | https://peerj.com/articles/15129.pdf |
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