Cerebrospinal fluid metabolomics identifies 19 brain-related phenotype associations
Open Access
- 12 January 2021
- journal article
- research article
- Published by Springer Science and Business Media LLC in Communications Biology
- Vol. 4 (1), 1-11
- https://doi.org/10.1038/s42003-020-01583-z
Abstract
The study of metabolomics and disease has enabled the discovery of new risk factors, diagnostic markers, and drug targets. For neurological and psychiatric phenotypes, the cerebrospinal fluid (CSF) is of particular importance. However, the CSF metabolome is difficult to study on a large scale due to the relative complexity of the procedure needed to collect the fluid. Here, we present a metabolome-wide association study (MWAS), which uses genetic and metabolomic data to impute metabolites into large samples with genome-wide association summary statistics. We conduct a metabolome-wide, genome-wide association analysis with 338 CSF metabolites, identifying 16 genotype-metabolite associations (metabolite quantitative trait loci, or mQTLs). We then build prediction models for all available CSF metabolites and test for associations with 27 neurological and psychiatric phenotypes, identifying 19 significant CSF metabolite-phenotype associations. Our results demonstrate the feasibility of MWAS to study omic data in scarce sample types.Keywords
This publication has 119 references indexed in Scilit:
- Identification of Altered Metabolic Pathways in Plasma and CSF in Mild Cognitive Impairment and Alzheimer’s Disease Using MetabolomicsPLOS ONE, 2013
- Genome-wide association study identifies multiple loci influencing human serum metabolite levelsNature Genetics, 2012
- Gut flora metabolism of phosphatidylcholine promotes cardiovascular diseaseNature, 2011
- LocusZoom: regional visualization of genome-wide association scan resultsBioinformatics, 2010
- METAL: fast and efficient meta-analysis of genomewide association scansBioinformatics, 2010
- A Branched-Chain Amino Acid-Related Metabolic Signature that Differentiates Obese and Lean Humans and Contributes to Insulin ResistanceCell Metabolism, 2009
- Metabolomic profiles delineate potential role for sarcosine in prostate cancer progressionNature, 2009
- N-acylphosphatidylethanolamine, a Gut- Derived Circulating Factor Induced by Fat Ingestion, Inhibits Food IntakeCell, 2008
- Identification of a Lipokine, a Lipid Hormone Linking Adipose Tissue to Systemic MetabolismCell, 2008
- PLINK: A Tool Set for Whole-Genome Association and Population-Based Linkage AnalysesAmerican Journal of Human Genetics, 2007