Depression and Inflammatory Bowel Disease: A Bidirectional Two-sample Mendelian Randomization Study
Background and Aims
Observational studies have suggested a bidirectional association between depression and inflammatory bowel disease [IBD], including Crohn’s disease [CD] and ulcerative colitis [UC]. However, it remains unclear whether the observed associations are causal due to the difficulties of determining sequential temporality. We investigated the association between depression and IBD by using bidirectional two-sample Mendelian randomization [MR].
Methods
Independent genetic variants for depression and IBD were selected as instruments from published genome-wide association studies [GWAS] among individuals of predominantly European ancestry. Summary statistics for instrument–outcome associations were retrieved from three separate databases for both depression [Psychiatric Genomics Consortium, FinnGen and UK Biobank] and IBD [the largest GWAS meta-analysis, FinnGen and UK Biobank], respectively. MR analyses included the inverse-variance-weighted method, weighted-median estimator, MR-Egger regression, and sensitivity analyses of Steiger filtering and MR PRESSO. From either direction, analyses were performed per outcome database and were subsequently meta-analysed using a fixed-effect model.
Results
Genetically predicted depression [per log-odds ratio increase] was associated with a higher risk of IBD; odds ratios [95% confidence interval] for IBD, CD and UC were 1.20 [1.05, 1.36], 1.29 [1.07, 1.56] and 1.22 [1.01, 1.47] in a combined sample size of 693 183 [36 507 IBD cases], 212 172 [13 714 CD cases] and 219 686 [15 691 UC cases] individuals, respectively. In contrast, no association was observed between genetically influenced IBD and depression in 534 635 individuals [71 466 depression cases].
Conclusions
Our findings corroborated a causal association of depression on IBD, which may impact the clinical decision on the management of depression in patients with IBD. Though our results did not support a causal effect of IBD on depression, further investigations are needed to clarify the effect of IBD activity on depression [with different symptomology].
Top-30
Journals
|
1
2
3
4
5
6
7
8
|
|
|
Medicine (United States)
8 publications, 6.61%
|
|
|
Journal of Clinical Medicine
5 publications, 4.13%
|
|
|
Genes
4 publications, 3.31%
|
|
|
Frontiers in Genetics
4 publications, 3.31%
|
|
|
Frontiers in Immunology
4 publications, 3.31%
|
|
|
International Journal of Molecular Sciences
3 publications, 2.48%
|
|
|
Frontiers in Psychiatry
3 publications, 2.48%
|
|
|
Frontiers in Neurology
3 publications, 2.48%
|
|
|
Journal of Affective Disorders
3 publications, 2.48%
|
|
|
Frontiers in Endocrinology
3 publications, 2.48%
|
|
|
Inflammatory Bowel Diseases
3 publications, 2.48%
|
|
|
Scientific Reports
3 publications, 2.48%
|
|
|
International Immunopharmacology
3 publications, 2.48%
|
|
|
Translational Psychiatry
2 publications, 1.65%
|
|
|
Inflammopharmacology
2 publications, 1.65%
|
|
|
World Journal of Gastroenterology
2 publications, 1.65%
|
|
|
World Journal of Clinical Cases
2 publications, 1.65%
|
|
|
Journal of Crohn's and Colitis
2 publications, 1.65%
|
|
|
Heliyon
2 publications, 1.65%
|
|
|
Life
2 publications, 1.65%
|
|
|
JAMA Psychiatry
1 publication, 0.83%
|
|
|
Journal of Alzheimer's Disease
1 publication, 0.83%
|
|
|
Frontiers in Oncology
1 publication, 0.83%
|
|
|
Schizophrenia
1 publication, 0.83%
|
|
|
Nature Reviews Gastroenterology and Hepatology
1 publication, 0.83%
|
|
|
European Journal of Nutrition
1 publication, 0.83%
|
|
|
General Hospital Psychiatry
1 publication, 0.83%
|
|
|
Pharmaceuticals
1 publication, 0.83%
|
|
|
Internal and Emergency Medicine
1 publication, 0.83%
|
|
|
1
2
3
4
5
6
7
8
|
Publishers
|
5
10
15
20
25
|
|
|
Frontiers Media S.A.
22 publications, 18.18%
|
|
|
Springer Nature
22 publications, 18.18%
|
|
|
MDPI
17 publications, 14.05%
|
|
|
Elsevier
13 publications, 10.74%
|
|
|
Ovid Technologies (Wolters Kluwer Health)
9 publications, 7.44%
|
|
|
Oxford University Press
7 publications, 5.79%
|
|
|
Taylor & Francis
5 publications, 4.13%
|
|
|
Baishideng Publishing Group
4 publications, 3.31%
|
|
|
Wiley
4 publications, 3.31%
|
|
|
Cold Spring Harbor Laboratory
3 publications, 2.48%
|
|
|
Research Square Platform LLC
2 publications, 1.65%
|
|
|
American Medical Association (AMA)
1 publication, 0.83%
|
|
|
SAGE
1 publication, 0.83%
|
|
|
Media Sphere Publishing House
1 publication, 0.83%
|
|
|
Proceedings of the National Academy of Sciences (PNAS)
1 publication, 0.83%
|
|
|
BMJ
1 publication, 0.83%
|
|
|
Science in China Press
1 publication, 0.83%
|
|
|
IMR Press
1 publication, 0.83%
|
|
|
Cambridge University Press
1 publication, 0.83%
|
|
|
5
10
15
20
25
|
- We do not take into account publications without a DOI.
- Statistics recalculated weekly.