Assessing causal links between metabolic traits, inflammation and schizophrenia: a univariable and multivariable, bidirectional Mendelian-randomization study.
Bayes Theorem
Biomarkers
C-Reactive Protein
/ analysis
Genetic Predisposition to Disease
Humans
Inflammation
/ epidemiology
Leucine
/ blood
Lipids
/ blood
Lipoproteins, VLDL
/ blood
Mendelian Randomization Analysis
Phenotype
Polymorphism, Single Nucleotide
Risk Factors
Schizophrenia
/ blood
Triglycerides
/ blood
C-reactive protein
Mendelian randomization
blood metabolites
schizophrenia
Journal
International journal of epidemiology
ISSN: 1464-3685
Titre abrégé: Int J Epidemiol
Pays: England
ID NLM: 7802871
Informations de publication
Date de publication:
01 10 2019
01 10 2019
Historique:
accepted:
07
08
2019
pubmed:
11
9
2019
medline:
21
4
2020
entrez:
11
9
2019
Statut:
ppublish
Résumé
Blood immunoreactive biomarkers, such as C-reactive protein (CRP), and metabolic abnormalities have been associated with schizophrenia. Studies comprehensively and bidirectionally probing possible causal links between such blood constituents and liability to schizophrenia are lacking. To disentangle putative causal links between CRP blood levels and schizophrenia in both directions, we conducted multiple univariable Mendelian-randomization (MR) analyses, ranging from fixed-effect to inverse variance-weighted (IVW), weighted-median, MR Egger and generalized summary-data-based Mendelian-randomization (GSMR) models. To prioritize metabolic risk factors for schizophrenia, a novel multivariable approach was applied: multivariable Mendelian-randomization-Bayesian model averaging (MR-BMA). All forward univariable MR analyses consistently showed that CRP has a protective effect on schizophrenia, whereas reverse MR analyses consistently suggested absent causal effects of schizophrenia liability on CRP blood levels. Using MR-BMA, as the top protective factors for schizophrenia we prioritized leucine and as the prime risk-factor triglycerides in medium very-low-density lipoprotein (VLDL). The five best-performing MR-BMA models provided one additional risk factor: triglycerides in large VLDL; and two additional protective factors: citrate and lactate. Our results add to a growing body of literature hinting at metabolic changes-in particular of triglycerides-independently of medication status in schizophrenia. We also highlight the absent effects of genetic liability to schizophrenia on CRP levels.
Sections du résumé
BACKGROUND
Blood immunoreactive biomarkers, such as C-reactive protein (CRP), and metabolic abnormalities have been associated with schizophrenia. Studies comprehensively and bidirectionally probing possible causal links between such blood constituents and liability to schizophrenia are lacking.
METHODS
To disentangle putative causal links between CRP blood levels and schizophrenia in both directions, we conducted multiple univariable Mendelian-randomization (MR) analyses, ranging from fixed-effect to inverse variance-weighted (IVW), weighted-median, MR Egger and generalized summary-data-based Mendelian-randomization (GSMR) models. To prioritize metabolic risk factors for schizophrenia, a novel multivariable approach was applied: multivariable Mendelian-randomization-Bayesian model averaging (MR-BMA).
RESULTS
All forward univariable MR analyses consistently showed that CRP has a protective effect on schizophrenia, whereas reverse MR analyses consistently suggested absent causal effects of schizophrenia liability on CRP blood levels. Using MR-BMA, as the top protective factors for schizophrenia we prioritized leucine and as the prime risk-factor triglycerides in medium very-low-density lipoprotein (VLDL). The five best-performing MR-BMA models provided one additional risk factor: triglycerides in large VLDL; and two additional protective factors: citrate and lactate.
CONCLUSIONS
Our results add to a growing body of literature hinting at metabolic changes-in particular of triglycerides-independently of medication status in schizophrenia. We also highlight the absent effects of genetic liability to schizophrenia on CRP levels.
Identifiants
pubmed: 31504541
pii: 5557835
doi: 10.1093/ije/dyz176
pmc: PMC7070229
doi:
Substances chimiques
Biomarkers
0
Lipids
0
Lipoproteins, VLDL
0
Triglycerides
0
very low density lipoprotein triglyceride
0
C-Reactive Protein
9007-41-4
Leucine
GMW67QNF9C
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1505-1514Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© The Author(s) 2019; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association.
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