Assessment of Bidirectional Relationships between Mental Illness and Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study
Abstract
:1. Introduction
2. Methods
2.1. Study Design
2.2. Selection of Instrumental Variables
2.3. Data Sources
2.4. MR Analysis
2.5. Statistical Analysis
3. Results
3.1. Causal Effect of Bipolar Disorder on RA
3.2. Causal Effect of Broad Depression, Major Depression, and Anxiety on RA
3.3. Causal Effects of RA on Bipolar Disorder, Broad Depression, Major Depression, and Anxiety
4. Discussion
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
References
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Phenotype | GWAS Reference | Case Ascertainment | Ethnicity | Sample Size |
---|---|---|---|---|
Bipolar disorder | Mullins, N et al., 2021 [32] | Cases were individuals diagnosed with the international consensus criteria for defined bipolar disorder (The Diagnostic and Statistical Manual of Mental Disorders-IVS, International Classification of diseases-9, or International Classification of diseases-10), using structured diagnostic interviews, clinician-managed checklists, or medical history reviews. | European ancestry | 41,917 cases and 371,549 controls |
Broad depression | Howard, D.M et al., 2018 [33] | Cases were individuals included by self-reported, help-seeking behavior for mental health difficulties. | European ancestry | 113,769 cases and 208,811 controls |
Major depression | Howard, D.M, et al., 2019 [34] | Cases were ascertained by structured diagnostic interviews, national inpatient electronic records, self-reported major depression symptoms or treatment or electronic records, and self-reported diagnosis or treatment for clinical depression by a medical professional. | European ancestry | 246,363 cases and 561,190 controls |
Anxiety | Otowa, T et al., 2016 [39] | Cases were individuals diagnosed with anxiety by a psychiatrist. It satisfies the genetic effects shared across the five core anxiety disorders: generalized anxiety disorder (GAD), panic disorder (PD), social phobia, agoraphobia, and specific phobia. | European ancestry | 7016 cases and 14,745 controls |
RA | Okada, Y et al., 2014 [36] | All cases met the diagnostic criteria of RA of the American Rheumatology Association in 1987 [40] or were diagnosed with RA by experts. | European ancestry | 14,361 cases and 43,923 controls |
Exposure | Outcome | Method | No. of SNPs | OR (95% CI) | p-Value |
---|---|---|---|---|---|
Broad depression | Rheumatoid arthritis | Inverse variance weighted | 2 | 11.76 (0.23, 600.62) | 0.22 |
Major depression | Rheumatoid arthritis | Inverse variance weighted | 60 | 1.14 (0.87, 1.50) | 0.35 |
MR-Egger | 60 | 0.66 (0.24, 1.85) | 0.44 | ||
Weighted median | 60 | 1.08 (0.76, 1.55) | 0.66 | ||
Simple mode | 60 | 0.61 (0.27, 1.35) | 0.23 | ||
Weighted mode | 60 | 0.83 (0.49, 1.41) | 0.49 | ||
Anxiety | Rheumatoid arthritis | Inverse variance weighted | 7 | 1.12 (0.89, 1.40) | 0.35 |
MR-Egger | 7 | 0.80 (0.19, 3.40) | 0.78 | ||
Weighted median | 7 | 1.19 (0.92, 1.55) | 0.19 | ||
Simple mode | 7 | 1.16 (0.75, 1.78) | 0.52 | ||
Weighted mode | 7 | 1.19 (0.79, 1.78) | 0.43 |
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Xiang, S.; Wang, R.; Hua, L.; Song, J.; Qian, S.; Jin, Y.; Zhang, B.; Ding, X. Assessment of Bidirectional Relationships between Mental Illness and Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study. J. Clin. Med. 2023, 12, 944. https://doi.org/10.3390/jcm12030944
Xiang S, Wang R, Hua L, Song J, Qian S, Jin Y, Zhang B, Ding X. Assessment of Bidirectional Relationships between Mental Illness and Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study. Journal of Clinical Medicine. 2023; 12(3):944. https://doi.org/10.3390/jcm12030944
Chicago/Turabian StyleXiang, Shate, Rongyun Wang, Lijiangshan Hua, Jie Song, Suhai Qian, Yibo Jin, Bingyue Zhang, and Xinghong Ding. 2023. "Assessment of Bidirectional Relationships between Mental Illness and Rheumatoid Arthritis: A Two-Sample Mendelian Randomization Study" Journal of Clinical Medicine 12, no. 3: 944. https://doi.org/10.3390/jcm12030944