ArticleBiological psychiatry2023
Metabolomic Investigation of Major Depressive Disorder Identifies a Potentially Causal Association With Polyunsaturated Fatty Acids.
Article in Biological psychiatry, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 48 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
48 citing papers in PubMed, 1 synthesis or guideline pooled it, 84 citations in OpenAlex.
- Causal role of genetically predicted impairment of branched-chain amino acid catabolism on insulin secretion and insulin resistance in type 2 diabetes.Diabetes, obesity & metabolism · 2026Pooled it
- Genome-Wide Association of Genetic Variants with Intestinal Cholesterol Absorption Markers in a European Population.Nutrients · 2026Article
- Mendelian-Randomization Study Reveals Causal Relationships Between Blood Metabolites and Psychiatric Disorders.Schizophrenia bulletin · 2026Article
- Divergent Patterns of Genetic Overlap Between Severe Mental Disorders and Metabolic Markers.The American journal of psychiatry · 2026Article
- Metabolomic ageing across mental and behavioural disorders.BMJ mental health · 2026Article
- A genetic atlas of relationships between circulating metabolites and liability to psychiatric conditions.Molecular psychiatry · 2026Article
- Shared genetic architecture and pathways linking major depressive disorder and autoimmune thyroid disease: insights from common and rare variants.Translational psychiatry · 2026Article
- Amino Acid-Fatty Acid Profile as a Novel Predictive Method in the Assessment of Diagnosis and Treatment Efficacy of Anxiety-Related Disorders and Mood Disorders.International journal of molecular sciences · 2026Review
- Mendelian Randomization Identifies Lipidomic Signatures of Depression Risk That Are Partly Reflected in Cortisol-Induced Membrane Remodeling and Modulated by St. John's Wort Extract (Ze 117).International journal of molecular sciences · 2026Article
- Causal statistical association between remnant cholesterol and coronary heart disease: genetic insights into the PSRC1-CELSR2-SORT1 gene cluster.Journal of lipid research · 2026Article
- Astrocyte fatty acid metabolism as a driver of risk for major depressive disorder.Nature communications · 2026Article
- Blood biomarkers and breed genetics of aging in pet dogs.bioRxiv : the preprint server for biology · 2026Article
- Immunometabolic blood biomarkers of developmental trajectories of depressive symptoms: findings from the ALSPAC birth cohort.Molecular psychiatry · 2026Article
- Circulating fatty acids and osteoarthritis: evidence from observational and genetic analyses.The British journal of nutrition · 2026Article
- Clinical efficacy and multi-omics analysis of Si-Ni-San for depression treatment in breast cancer patients: a randomized, double-blind, placebo-controlled, crossover trial.Chinese medicine · 2026Article
- Lipopolysaccharide induced mouse depression model can better simulate changes in peripheral blood FFAs in alMDD.PloS one · 2026Article
- Polyunsaturated Fatty Acids and Skin Cancer: Two-Sample Mendelian Randomization Study.Annals of dermatology · 2025Article
- GWAS and multi-omics integrative analysis reveal novel loci and their molecular mechanisms for circulating fatty acids.HGG advances · 2025Article
- Analysis of Genomic and Transcriptomic Data Revealed Key Genes and Processes in the Development of Major Depressive Disorder.International journal of molecular sciences · 2025Article
- Genetic architecture of plasma metabolome in 254,825 individuals.Nature communications · 2025Article
Corrections and comments
- Erratum issuedErratum.2024
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMetabolic differences have been reported between individuals with and without major depressive disorder (MDD), but their consistency and causal relevance have been unclear.
methodsWe conducted a metabolome-wide association study of MDD with 249 metabolomic measures available in the UK Biobank (n = 29,757). We then applied two-sample bidirectional Mendelian randomization and colocalization analysis to identify potentially causal relationships between each metabolite and MDD.
resultsA total of 191 metabolites tested were significantly associated with MDD (false discovery rate-corrected p < .05), which decreased to 129 after adjustment for likely confounders. Lower abundance of omega-3 fatty acid measures and a higher omega-6 to omega-3 ratio showed potentially causal effects on liability to MDD. There was no evidence of a causal effect of MDD on metabolite levels. Furthermore, genetic signals associated with docosahexaenoic acid colocalized with loci associated with MDD within the fatty acid desaturase gene cluster. Post hoc Mendelian randomization of gene-transcript abundance within the fatty acid desaturase cluster demonstrated a potentially causal association with MDD. In contrast, colocalization analysis did not suggest a single causal variant for both transcript abundance and MDD liability, but rather the likely existence of two variants in linkage disequilibrium with one another.
conclusionsOur findings suggest that decreased docosahexaenoic acid and increased omega-6 to omega-3 fatty acids ratio may be causally related to MDD. These findings provide further support for the causal involvement of fatty acids in MDD.
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