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Results from the LMER models with the same effect size direction in the discovery and replication cohorts were then meta-analysed using fixed-effects meta-analysis implemented via the R package metafor (v.4.40)

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TMA-containing compound assay Trimethylamine-containing compounds were extracted from 50 l of plasma, 50 l of whole liver homogenate or from 100 l of whole brain homogenate (without the cerebellum and olfactory bulbs) by adding 10 volumes of ACN and spiking the samples with 5 l of IS mix containing 12 M d9-TMAO (CIL), 649 nM d9-TMA (CDN Isotopes), 6 M d3-L-carnitine (CIL), 329 nM d9-crotonobetaine (see Koeth et al., 2014) and 5 M d9-TML (Santa Cruz Biotechnology) at the beginning of the extraction