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Additional file 2 of Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders
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Additional file 2 of Evaluating metabolome-wide causal effects on risk for psychiatric and neurodegenerative disorders

Lachlan Gilchrist, Julian Mutz, Pirro Hysi, Cristina Legido-Quigley, Sulev Kõks, Cathryn M. Lewis and Petroula Proitsi
Springer Nature
03/06/2025
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CC BY V4.0 Open Access

Abstract

Biochemistry Biological Sciences not elsewhere classified Biotechnology Cell Biology Chemical Sciences not elsewhere classified Medicine Molecular Biology Neuroscience Science Policy
Additional file 2. Table S1: A Linkage Disequilibrium Score Regression (LDSC) calculated genetic correlation (rg) results with standard errors, p-values and FDR corrected p-values; Table S2: Data fields from the UK Biobank used to ascertain first occurrences of this studies respective psychiatric and neurodegenerative disorder outcomes; Table S3: IVW-MR results for all metabolite-neuropsychiatric outcome pairs calculated in this study; Table S4: Sensitivity test results for all metabolite-outcome pairs with IVW-MR significant at p_FDR < 0.05 in our primary Mendelian randomisation analysis; Table S5: Reverse MR estimates for the effects of neuropsychiatric outcomes on metabolites passing sensitivity analyses; Table S6: MR-Egger intercept tests for metabolites with causal effects on psychiatric/neurodegenerative risk and passing sensitivity analyses; Table S7: Cochran's Q heterogeneity tests for metabolites with causal effects on psychiatric/neurodegenerative risk and passing sensitivity analyses; Table S8: Leave-one-out outlier tests for metabolites with causal effects on psychiatric/neurodegenerative risk and passing sensitivity analyses; Table S9: Metabolic pathways for polygenic metabolites with causal effects on psychiatric/neurodegenerative disorders and passing sensitivity analyses; Table S10: Metabolic pathways for single instrument metabolites with causal effects on psychiatric/neurodegenerative disorders and passing sensitivity analyses; Table S11 - LD matrix for influential outlying instruments in the FADS gene cluster implicated in LOO analysis; Table S12: Re-calculated Wald ratio estimates for metabolites with single influential instruments, calculated using the influential instrument for that metabolite only; Table S13: Re-calculated IVW-MR estimates for polygenic metabolites following mt-COJO conditional analysis of the outcome phenotype; Table S14: LDSC calculated genetic correlation matrix for polygenic metabolites, calculated as a filtering step in MR-BMA ; Table S15: MR-BMA results, with the marginal inclusion probability for each metabolite following multivariable analysis in each respective outcome; Table S16: Polygenic risk score results testing the association between MR-BMA prioritised metabolites and their respective psychiatric/neurodegenerative outcome identified in MR analysis; Table S17: Colocalisation results testing for the presence of a shared causal variants between metabolites and their respective psychiatric/neurodegenerative outcomes in regions of single influential variants identified in LOO MR analysis; Table S18: Table of linoleic and arachidonic containing metabolites and their direction of effect in the Wald ratio tests; Table S19: Genes in the regions with suggestive colocalisation between a metabolite and neuropsychiatric outcome; Table S20: Colocalisation results testing for the presence of a shared causal variants between metabolites, psychiatric/neurodegenerative outcomes and gene expression eQTLs in regions where evidence of colocalisation was identified between a metabolite and neuropsychiatric outcome; Table S21: Results of SMR follow-up analysis for SPRYD4 gene expression, Alzheimer's disease and the ratio of histidine-to-glutamine; Table S22: MR results of the effect of glutamine on Alzheimer's disease; Table S23: Leave-one-out analysis for the effect of glutamine on Alzheimer's disease; Table S24: Colocalisation results between glutamine and Alzheimer's and between glutamine and SPRYD4 expression in the region of the influential variant identified in LOO analysis; Table S25: Follow-up SMR results for SPRYD4 expression and glutamine.

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