Mendelian randomization provides no evidence for a causal role in the bidirectional relationship between depression and multiple sclerosis.
Mendelian randomization
Multiple sclerosis
genetic epidemiology
major depressive disorder
Journal
Multiple sclerosis (Houndmills, Basingstoke, England)
ISSN: 1477-0970
Titre abrégé: Mult Scler
Pays: England
ID NLM: 9509185
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
pubmed:
17
2
2021
medline:
28
1
2022
entrez:
16
2
2021
Statut:
ppublish
Résumé
Major depressive disorder (MDD) is common in multiple sclerosis (MS) and its incidence rises before MS diagnosis. However, the causality and direction of this association remain unclear. The objective is to investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR). We selected genetic instruments associated with risk of MDD ( We found no effect of genetic liability to MDD on the odds of MS (OR = 1.07/doubling in odds, 95% CI = 0.90-1.28). Similarly, our findings did not support a causal effect of genetic liability to MS on MDD (OR = 1.00/doubling in odds, 95% CI = 0.99-1.01). Despite heterogeneity, sensitivity analyses indicated that bias from pleiotropy was unlikely. Conversely, genetic predisposition toward higher BMI increased the odds of MS (OR = 1.34/SD increase, 95% CI = 1.09-1.65) and MDD (OR = 1.08, 95% CI = 1.01-1.15). This study does not support a causal association between MDD genetic liability and MS susceptibility, and vice versa. Genetic evidence suggesting commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis.
Sections du résumé
BACKGROUND
Major depressive disorder (MDD) is common in multiple sclerosis (MS) and its incidence rises before MS diagnosis. However, the causality and direction of this association remain unclear.
OBJECTIVE
The objective is to investigate the bidirectional relationship between MS and MDD using Mendelian randomization (MR).
METHODS
We selected genetic instruments associated with risk of MDD (
RESULTS
We found no effect of genetic liability to MDD on the odds of MS (OR = 1.07/doubling in odds, 95% CI = 0.90-1.28). Similarly, our findings did not support a causal effect of genetic liability to MS on MDD (OR = 1.00/doubling in odds, 95% CI = 0.99-1.01). Despite heterogeneity, sensitivity analyses indicated that bias from pleiotropy was unlikely. Conversely, genetic predisposition toward higher BMI increased the odds of MS (OR = 1.34/SD increase, 95% CI = 1.09-1.65) and MDD (OR = 1.08, 95% CI = 1.01-1.15).
CONCLUSION
This study does not support a causal association between MDD genetic liability and MS susceptibility, and vice versa. Genetic evidence suggesting commonality of obesity to both conditions may partly explain the increased incidence of depression pre-MS diagnosis.
Identifiants
pubmed: 33591230
doi: 10.1177/1352458521993075
pmc: PMC8364919
mid: NIHMS1724575
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2077-2084Subventions
Organisme : NIMH NIH HHS
ID : K01 MH121582
Pays : United States
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