Mediation-adjusted multivariable Mendelian randomisation study identified novel metabolites related to mental health
BackgroundFrom the pathway perspective, metabolites have the potential to improve knowledge about the aetiology of psychiatric diseases. Previous studies suggested a link between specific blood metabolites and mental disorders, but some Mendelian randomisation (MR) studies in particular are insuffic...
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| Vydáno v: | BMJ mental health Ročník 27; číslo 1; s. e301230 |
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| Hlavní autoři: | , |
| Médium: | Journal Article |
| Jazyk: | angličtina |
| Vydáno: |
England
BMJ Publishing Group Ltd, Royal College of Psychiatrists and British Psychological Society
02.10.2024
BMJ Publishing Group LTD BMJ Publishing Group |
| Témata: | |
| ISSN: | 2755-9734, 2755-9734 |
| On-line přístup: | Získat plný text |
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| Shrnutí: | BackgroundFrom the pathway perspective, metabolites have the potential to improve knowledge about the aetiology of psychiatric diseases. Previous studies suggested a link between specific blood metabolites and mental disorders, but some Mendelian randomisation (MR) studies in particular are insufficient for various reasons.ObjectiveThis study focused on bias assessment due to interdependencies between metabolites and psychiatric mediation effects.MethodsIn a multistep framework containing network and multivariable MR, direct effects of 21 mutually adjusted metabolites on 8 psychiatric disorders were estimated based on summary statistics of genome-wide association studies from multiple resources. Robust inverse-variance weighted models were used in primary analyses. Several sensitivity analyses were performed to assess different patterns of pleiotropy and weak instrument bias. Estimates for the same phenotypes from different resources were pooled using fixed effect meta-analysis models.FindingsAfter adjusting for mediation effects, genetically predicted metabolite levels of six metabolites of lipid, amino acid and cofactors pathways were directly associated with overall six mental disorders (attention-deficit/hyperactivity disorder, bipolar disorder, anorexia nervosa, depression, post-traumatic stress disorder and schizophrenia). Point estimates ranged from −0.45 (95% CI −0.67; −0.24, p=1.0×104) to 1.78 (95% CI 0.85; 2.71, p=0.006). No associations were found with anxiety and suicide attempt.ConclusionsThis study provides insights into new metabolic pathways that seems to be causally related to certain mental disorders.Clinical implicationsFurther studies are needed to investigate whether the identified associations are effects of the metabolites itself or the biochemical pathway regulating the metabolites. |
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| Bibliografie: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23 Additional supplemental material is published online only. To view, please visit the journal online (https://doi.org/10.1136/bmjment-2024-301230). Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise. None declared. |
| ISSN: | 2755-9734 2755-9734 |
| DOI: | 10.1136/bmjment-2024-301230 |